Search

Background: Children with a compromised inferior vena cava (IVC) were previously considered unsuitable for kidney transplantation because of the technical difficulties and the increased risk of graft thrombosis secondary to inadequate renal venous outflow., Methods: We conducted a retrospective study of 11 transplants in 9 patients with end-stage renal disease and thrombosed IVCs who received adult kidney allografts between 2000 and 2015. The mean age at transplantation was 7.5 ± 3.5 years. A pretransplant diagnosis of the IVC thrombosis was made in 7 patients by magnetic resonance imaging and computerized tomography, whereas there were 2 instances of intraoperative discovery of the IVC thrombosis., Results: In the early cases, a kidney was placed intraperitoneally at the right iliac fossa with a venous anastomosis to the patent segment of the suprarenal IVC. After 2008, however, 6 adult-sized kidneys were subsequently placed in the left orthotopic position. Venous drainage was attained to the infrahepatic IVC (n = 3), left native renal vein (n = 2), and ascending lumbar vein (n = 1). Moreover, a venous bypass was created between the graft and the splenic vein in 2 children who showed high return pressure after the vessel was declamped. The mean glomerular filtration rate of the functioning 8 grafts 1 year posttransplant was 73.4 ± 20.4 mL/min per 1.73 m(2). Of note, 6 of the grafts have been functioning well, with a mean follow-up of 66 months. Both 1- and 5-year graft survival were 81.8%., Conclusions: Transplantation into the left orthotopic position and the revascularization methods are an effective set of surgical techniques that could potentially be adopted as safe and reliable transplant approaches in children with IVC thrombosis.

2.3-month-old (Case 1), one-month-old (Case 2) and 6-month-old (Case 3), Japanese Black calves presented with mild to severe wheezing. All calves had histories of dystocia at birth with breech presentation. Physical examination, thoracic radiography, endoscopy or computed tomography indicated wheezing associated with tracheal collapse and stenosis caused by perinatal rib fractures. Partial resection of the fractured first and second ribs was performed on all calves. The respiration in Cases 1 and 2 immediately improved after the surgery, while Case 3 required two weeks to improve. Cases 1 and 3 grew up healthy and were sold at auction, but Case 2 had a recurrence of wheezing at three months post-discharge and showed growth retarding. Partial costectomy may be an effective solution for control of respiration, however, further cases are required to discuss the criteria for surgical management and to obtain favorable postoperative prognosis in calves with tracheal collapse and stenosis caused by perinatal rib fractures.

Aim: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions., Methods: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis., Results: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region., Conclusion: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report.

Background: Non-photosynthetic chlorophyll (Chl) proteins called water-soluble Chl-binding proteins are distributed in Brassicaceae plants. Brassica oleracea WSCP (BoWSCP) and Lepidium virginicum WSCP (LvWSCP) are highly expressed in leaves and stems, while Arabidopsis thaliana WSCP (AtWSCP) and Raphanus sativus WSCP (RshWSCP) are highly transcribed in floral organs. BoWSCP and LvWSCP exist in the endoplasmic reticulum (ER) body. However, the subcellular localization of AtWSCP and RshWSCP is still unclear. To determine the subcellular localization of these WSCPs, we constructed transgenic plants expressing Venus-fused AtWSCP or RshWSCP., Results: Open reading frames corresponding to full-length AtWSCP and RshWSCP were cloned and ligated between the cauliflower mosaic virus 35S promoter and Venus, a gene encoding a yellow fluorescent protein. We introduced the constructs into A. thaliana by the floral dip method. We succeeded in constructing a number of transformants expressing Venus-fused chimeric AtWSCP (AtWSCP::Venus) or RshWSCP (RshWSCP::Venus). We detected fluorescence derived from the chimeric proteins using a fluorescence microscope system. In cotyledons, fluorescence derived from AtWSCP::Venus and RshWSCP::Venus was detected in spindle structures. The spindle structures altered their shape to a globular form under blue light excitation. In true leaves, the number of spindle structures was drastically reduced. These observations indicate that the spindle structure was the ER body., Conclusions: AtWSCP and RshWSCP have the potential for ER body targeting like BoWSCP and LvWSCP.

Twenty-five days after the disaster at the Fukushima Daiichi nuclear power plant in 2011, we collected samples of the green macroalga Bryopsis maxima from the Pacific coast of Japan. Bryopsis maxima is a unicellular, multinuclear, siphonous green macroalga. Radiation analysis revealed that B. maxima emitted remarkably high gamma radiation of (131)I, (134)Cs, (137)Cs, and (140)Ba as fission products of (235)U. Interestingly, B. maxima contained naturally occurring radionuclides derived from (226)Ra and (228)Ra. Analysis of element content revealed that B. maxima accumulates many ocean elements, especially high quantities of the alkaline earth metals Sr (15.9 g per dry-kg) and Ba (3.79 g per dry-kg), whereas Ca content (12.5 g per dry-kg) was lower than that of Sr and only 61 % of the mean content of 70 Japanese seaweed species. Time-course analysis determined the rate of radioactive (85)Sr incorporation into thalli to be approximately 0.13 g Sr per dry-kg of thallus per day. Subcellular fractionation of B. maxima cells showed that most of the (85)Sr was localized in the soluble fraction, predominantly in the vacuole or cytosol. Given that (85)Sr radioactivity was permeable through a dialysis membrane, the (85)Sr was considered to be a form of inorganic ion and/or bound with a small molecule. Precipitation analysis with sodium sulfate showed that more than 70% of the Sr did not precipitate as SrSO4, indicating that a proportion of the Sr may bind with small molecules in B. maxima.

Photoconvertible water-soluble chlorophyll-binding proteins, called Class I WSCPs, have been detected in Chenopodiaceae, Amaranthaceae and Polygonaceae plant species. To date, Chenopodium album WSCP (CaWSCP) is the only cloned gene encoding a Class I WSCP. In this study, we identified two cDNAs encoding Chenopodium ficifolium Class I WSCPs, CfWSCP1, and CfWSCP2. Sequence analyses revealed that the open reading frames of CfWSCP1 and CfWSCP2 were 585 and 588 bp, respectively. Furthermore, both CfWSCPs contain cystein2 and cystein30, which are essential for the chlorophyll-binding ability of CaWSCP. Recombinant CfWSCP1 and CfWSCP2, expressed in Escherichia coli as hexa-histidine fusion proteins (CfWSCP1-His and CfWSCP2-His), formed inclusion bodies; however, we were able to solubilize these using a buffer containing 8 M urea and then refold them by dialysis. The refolded CfWSCP1-His and CfWSCP2-His could bind chlorophylls and exhibited photoconvertibility, confirming that the cloned CfWSCPs are further examples of Class I WSCPs.

We investigated the effects of near-infrared irradiation on the photoconversion of Chenopodium album water-soluble chlorophyll-binding protein (CaWSCP) in the presence of sodium hydrosulfite and found a further photoconversion from CP742 to CP763, a novel form of CaWSCP. Interestingly, one-third of the absorption peak at 668 nm was recovered in CP763, but re-irradiation under oxidative conditions eliminated the photo convertibility of CaWSCP.

Chenopodium album has a non-photosynthetic chlorophyll protein known as the water-soluble chlorophyll (Chl)-binding protein (WSCP). The C. album WSCP (CaWSCP) is able to photoconvert the chlorin skeleton of Chl a into a bacteriochlorin-like skeleton. Reducing reagents such as β-mercaptoethanol or dithiothreitol inhibit photoconversion, indicating that S-S bridge(s) in CaWSCP are quite important for it. Recently, we found that the mature region of CaWSCP contains five cysteine residues; Cys2, Cys30, Cys48, Cys63, and Cys144. To identify which cysteine residues are involved in the photoconversion, we generated five mutants (C2S, C30S, C48S, C63S, and C144S) by site-directed mutagenesis. Interestingly, C48S, C63S, and C144S mutants showed the same Chl-binding activity and photoconvertibility as those of the recombinant wild-type CaWSCP-His, while the C2S and C30S mutants completely lost Chl-binding activity. Our findings indicated that the S-S bridge between Cys2 and Cys30 in each CaWSCP subunit is essential for Chl-binding activity.

Urothelial carcinoma (UC) is an extremely common type of cancer that occurs in the bladder. It has a particularly high rate of recurrence. Therefore, preclinical studies using animal models are essential to determine effective forms of treatment. In the present study, in order to establish an orthotopic bladder UC animal model with clinical relevance, the effects of preconditioning methods on properties of the developed tumor were evaluated. The bladder cavity was pretreated with phosphate-buffered saline (PBS), acid-base, trypsin (TRY) or poly (L-lysine) (PLL) and then rat UC cells (AY-27) (4×10 6 cells) were inoculated. The results demonstrated that, two weeks later, the tumorigenic rate (88%) and tumor count (2.3 per rat) were not significantly different among the preconditioning methods, whereas tumor volume and invasion depth into bladder tissue were significantly different. Average tumor volumes were >50 mm 3 in the PBS and acid-base-treated groups and <10 mm 3 in the TRY- and PLL-treated groups. The percentage of invasive tumors (T2 or more advanced stage) was ∼75% of total tumors in the PBS- and acid-base-treated groups, whereas the percentages were reduced in the TRY- and PLL-treated groups (58 and 32%, respectively). Non-invasive tumors (Ta or T1) accounted for 54% of tumors in the PLL-treated group, which was 2-5-fold higher than the percentages in the remaining groups. Properties of the developed tumor in the rat orthotopic UC model were different depending on preconditioning methods. Therefore, different animal models suitable for a discrete preclinical examination may be established by using the appropriate preconditioning condition.

Various plants possess non-photosynthetic, hydrophilic chlorophyll (Chl) proteins called water-soluble Chl-binding proteins (WSCPs). WSCPs are categorized into two classes; Class I (photoconvertible type) and Class II (non-photoconvertible type). Among Class II WSCPs, only Lepidium virginicum WSCP (LvWSCP) exhibits a low Chl a/b ratio compared with that found in the leaf. Although the physicochemical properties of LvWSCP have been characterized, its molecular properties have not yet been documented. Here, we report the characteristics of the LvWSCP gene, the biochemical properties of a recombinant LvWSCP, and the intracellular localization of LvWSCP. The cloned LvWSCP gene possesses a 669-bp open reading frame. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis revealed that the precursor of LvWSCP contains both N- and C-terminal extension peptides. RT-PCR analysis revealed that LvWSCP was transcribed in various tissues, with the levels being higher in developing tissues. A recombinant LvWSCP and hexa-histidine fusion protein (LvWSCP-His) could remove Chls from the thylakoid in aqueous solution and showed an absorption spectrum identical to that of native LvWSCP. Although LvWSCP-His could bind both Chl a and Chl b, it bound almost exclusively to Chl b when reconstituted in 40 % methanol. To clarify the intracellular targeting functions of the N- and C-terminal extension peptides, we constructed transgenic Arabidopsis thaliana lines expressing the Venus protein fused with the LvWSCP N- and/or C-terminal peptides, as well as Venus fused at the C-terminus of LvWSCP. The results showed that the N-terminal peptide functioned in ER body targeting, while the C-terminal sequence did not act as a trailer peptide.

Immunoglobulin (Ig) G4-related disease is a novel disease entity characterized by diffuse lymphoplasmacytic infiltrates and the presence of abundant IgG4-positive plasma cells in extensive fibrosis, frequently associated with tumorous swelling lesion and elevated serum IgG4 concentrations. Immunoglobulin G4-related disease has been described in almost every organ system but rarely affects the heart. We describe a rare case of IgG4-related disease of the heart causing aortic regurgitation and heart block in a 59-year-old woman. The excised lesion revealed a high ratio of IgG4-positive to IgG-positive plasma cells, providing a definite diagnosis of IgG4-related disease. The aortic valve was replaced using Manouguian technique, resulting in a favorable outcome., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We report an unusual case of bilateral ureteral polyps causing intermittent hydronephrosis, which developed extensively in the upper part of ureters. The patient was an 8-year-old male. He had several episodes of gross hematuria with right flank pain. Ultrasonography of the kidney showed mild bilateral hydronephrosis, while this finding was markedly aggravated in association with the onset of pain. Intravenous pyelogram and retrograde pyelogram revealed multiple filling defects in both upper parts of ureters. Since the diseased part of the ureter was wide (about 7 cm in length), a segmental resection of the right ureter with mobilization of the right kidney was performed, followed by end-to-end ureteral anastomosis. The pathological diagnosis was fibroepithelial polyps. Regarding the disease of contralateral ureter, no surgical treatment was performed because he had no clinical symptoms. Six years after the surgery, he again developed gross hematuria with left flank pain. Marked dilatation of the left renal pelvis was shown by ultrasonography, which suggested left intermittent hydronephrosis caused by ureteral polyps. He underwent a partial ureterectomy with mobilization of the left kidney for the left ureteral disease. No recurrence of polyps has been observed in the urinary tract since this surgery.

A water-soluble chlorophyll-binding protein (WSCP) is the single known instance of a putative chlorophyll (Chl) carrier in green plants. Recently the photoprotective function of WSCP has been demonstrated by EPR measurements; the light-induced singlet-oxygen formation of Chl in the WSCP tetramer is about four times lower than that of unbound Chl. This paper describes the crystal structure of the WSCP-Chl complex purified from leaves of Lepidium virginicum (Virginia pepperweed) to clarify the mechanism of its photoprotective function. The WSCP-Chl complex is a homotetramer comprising four protein chains of 180 amino acids and four Chl molecules. At the center of the complex one hydrophobic cavity is formed in which all of the four Chl molecules are tightly packed and isolated from bulk solvent. With reference to the novel Chl-binding mode, we propose that the photoprotection mechanism may be based on the inhibition of physical contact between the Chl molecules and molecular oxygen.

Purpose: Noninvasive and serial evaluation of tumor development and growth is important in an orthotopic animal bladder tumor model. However, to our knowledge a reliable method has not been established. We determined the usefulness of intravesical ultrasonography for tumor staging and volumetric assessment in an animal model., Materials and Methods: Tumors with various stages were formed in 20 female Fischer F344 rats by implanting AY-27 rat bladder carcinoma cells. Cells were implanted by instilling a suspension (4x10 cells) into the bladder cavity after urothelial denudation using hydrochloric acid or by directly injecting the cell suspension into the bladder wall. Tumor volume and invasion depth were measured by intravesical ultrasonography using an ultrathin 2.5Fr intraluminal ultrasound catheter via the urethra 7 to 10 days after cancer cell implantation. The rats were then sacrificed for histopathological examination., Results: All rats showed bladder tumors 7 to 10 days after cancer cell implantation, of which stages varied from superficial to advanced disease. Intravesical ultrasonography showed a clear cross-sectional view of all layers of the bladder wall and enabled visualization of bladder tumors (minimal 0.5 mm in diameter). This approach also provided an accurate diagnosis of tumor invasion into muscle layers and perivesical tissues with precise invasion depth and tumor size. The positive predictive ratio regarding tumor staging reached 85%. Repeat examinations were feasible without noticeable adverse effects., Conclusions: Intravesical ultrasonography is a reliable and appropriate noninvasive method for evaluating tumor stage and size in an orthotopic rat bladder tumor model.

The present study investigated cerebrospinal fluid (CSF) biomarkers for estimating degeneration of the central nervous system (CNS) in experimental dogs with GM1 gangliosidosis and preliminarily evaluated the efficacy of long-term glucocorticoid therapy for GM1 gangliosidosis using the biomarkers identified here. GM1 gangliosidosis, a lysosomal storage disease that affects the brain and multiple systemic organs, is due to an autosomal recessively inherited deficiency of acid beta-galactosidase activity. Pathogenesis of GM1 gangliosidosis may include neuronal apoptosis and abnormal axoplasmic transport and inflammatory response, which are perhaps consequent to massive neuronal storage of GM1 ganglioside. In the present study, we assessed some possible CSF biomarkers, such as GM1 ganglioside, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and myelin basic protein (MBP). Periodic studies demonstrated that GM1 ganglioside concentration, activities of AST and LDH, and concentrations of NSE and MBP in CSF were significantly higher in dogs with GM1 gangliosidosis than those in control dogs, and their changes were well related with the months of age and clinical course. In conclusion, GM1 ganglioside, AST, LDH, NSE and MBP could be utilized as CSF biomarkers showing CNS degeneration in dogs with GM1 gangliosidosis to evaluate the efficacy of novel therapies proposed for this disease. In addition, we preliminarily treated an affected dog with long-term oral administration of prednisolone and evaluated the efficacy of this therapeutic trial using CSF biomarkers determined in the present study. However, this treatment did not change either the clinical course or the CSF biomarkers of the affected dog, suggesting that glucocorticoid therapy would not be effective for treating GM1 gangliosidosis.

Objective: Tubularized incised plate urethroplasty has become a popular technique for repairing distal and proximal hypospadias in many institutions. Dorsal inlay graft urethroplasty has been used in our institution since 2003 to reduce the risk of meatal stenosis. In the present study, we evaluated the results of the dorsal inlay graft procedure., Methods: A total of 28 patients with no deep groove and no severe curvature underwent one-stage urethroplasty using an inner preputial-based dorsal inlay graft. The medical records of all patients were retrospectively reviewed with regard to complication rate and cosmetic appearance., Results: Mean patient age at surgery was 21 months (range, 14 months to 4.6 years). Preoperatively the urethral meatus was coronal in two cases, distal shaft in 17, proximal shaft in six and penoscrotal in three. Nine patients required testosterone therapy before surgery. Mean operative time was 200 min (range, 154-249 min). Mean length of inlay graft was 20.9 mm (range, 12-30 mm). In all patients, a straight penis was achieved without dorsal plication of the corposa cavernosa, and the neomeatus with a slit-like appearance was positioned at the glans tip. At a mean of 22 months of follow up, a urethrocutaneous fistula developed in only one patient (3.6%), requiring repair surgery 6 months after urethroplasty. No patient had meatal stenosis, neourethral stricture or urethral diverticulum along the inlay graft., Conclusion: Dorsal inlay graft urethroplasty is an effective method for hypospadiac repair and leads to good cosmetic outcome with low risk of complications.

Recent studies have suggested that the alpha7 nicotinic acetylcholine receptors play important roles in learning and memory. Herein, we describe our research of the structure-activity relationships (SAR) in a series of (S)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin]-2'-ones bearing various bicyclic moieties to discover novel alpha7 receptor agonists. Through a number of SAR studies on the series, we have found out that inhibition of CYP 2D6 isozyme, which was a primary obstacle for the previously identified compound, was avoidable by the introduction of bicyclic moieties. Chemical optimization of the series led to the identification of a novel and potent alpha7 nicotinic acetylcholine receptor partial agonist 23. This compound not only possessed high binding affinity (K(i) = 3 nmol/L) toward the alpha7 receptor but also showed agonistic activity even at a concentration of 0.1 micromol/L. In addition, compound 23 improved cognition in several rat models, which might suggest the potential of the alpha7 receptor partial agonist for the treatment of neurological disorders including cognitive dysfunction.

The KINDL-questionnaire is able to measure degrees of health and adaptability in relation to quality of life (QOL) in children. The questionnaire can be completed by children, adolescents, and their parents (parent-version). We had translated Kid-KINDL questionnaire into Japanese as Questionnaire for Measuring QOL in Japanese Elementary School Children, and reported their reliability and validity. This study investigates Japanese elementary school version of the Kid-KINDL questionnaire scores consisting of 6 dimensions (4 items each;total score, 100) for children with developmental disorders without mental retardation including high-functioned pervasive developmental disorder, attention deficit/hyperactivity disorder and learning disorder, and the parent-version scores for their mothers. Twenty individuals in normal class and their mothers participated after informed consents were obtained. Their total QOL scores were significantly lower than those in control group. Four of 6 dimensions consisting of emotional well-being, self-esteem, family, friends and school had significantly lower points. Their mothers' points in total QOL scores and all dimensions except for family dimension were significantly lower than those in control group. In comparison of scores between children with mild developmental disorders and their mothers, children estimated lower in self-esteem and family dimensions instead mother estimated lower in health, emotional well-being and school dimensions. There was no difference in total scores between them. Children with mild developmental disorders and their mothers estimate lower points of QOL scores than those of the normal control group. There are different perceptions in 5 of 6 dimensions between the children and their mothers.

Nocardia species are gram-positive environmental saprophytes, but some cause the infectious disease nocardiosis. The complete genomic sequence of Nocardia farcinica IFM 10152 has been determined, and analyses indicated the presence of two different RNA polymerase beta subunit genes, rpoB and rpoB2, in the genome (J. Ishikawa, A. Yamashita, Y. Mikami, Y. Hoshino, H. Kurita, K. Hotta, T. Shiba, and M. Hattori, Proc. Natl. Acad. Sci. USA 101:14925-14930, 2004). These genes share 88.8% identity at the nucleotide level. Moreover, comparison of their amino acid sequences with those of other bacterial RpoB proteins suggested that the nocardial RpoB protein is likely to be rifampin (RIF) sensitive, whereas RpoB2 protein contains substitutions at the RIF-binding region that are likely to confer RIF resistance. Southern analysis indicated that rpoB duplication is widespread in Nocardia species and is correlated with the RIF-resistant phenotype. The introduction of rpoB2 by using a newly developed Nocardia-Escherichia coli shuttle plasmid vector and transformation system conferred RIF resistance to Nocardia asteroides IFM 0319T, which has neither RIF resistance nor rpoB duplication. Furthermore, unmarked rpoB2 deletion mutants of N. farcinica IFM 10152 showed no significant resistance to RIF. These results indicated the contribution of rpoB2 to RIF resistance in Nocardia species. Since this is the first example of genetic engineering of the Nocardia genome, we believe that this study, as well as our determination of the N. farcinica genome sequence, will be a landmark in Nocardia genetics.

Purpose: PAD-S31 (13,17-bis (1-carboxypropion) carbamoylethyl-3-ethenyl-8-ethoxyiminoethylidene-7-hydroxy-2,7,12,18-tetramethyl-porphyrin sodium) (Photochemical Co., Ltd., Okayama, Japan), 1 of the latest second-generation photosensitizers, has hydrophilic characteristics and excitation wavelengths of around 670 nm. Using an orthotopic rat bladder tumor model we investigated the biodistribution of PAD-S31 and assessed the antitumor effects of photodynamic therapy (PDT) with PAD-S31., Materials and Methods: An orthotopic rat bladder tumor was established by implanting AY-27 cells in the bladder wall. After intravenous PAD-S31 administration the accumulation of PAD-S31 in the tumor and normal bladder wall was investigated by a fluorometric technique. One or 3 hours after intravenous administration of PAD-S31 (5 mg/kg) bladder tumors in rats were transurethrally irradiated at 100 mW/cm with a light dose of 50 to 200 J/cm. The efficacy of PDT was evaluated 7 days later by observation with an ultrathin cystoscope and histopathological examination., Results: The ratio of PAD-S31 concentration in tumor tissue to that in normal bladder wall was more than 1 at all time points and it achieved a maximum (more than 10) 150 to 240 minutes after PAD-S31 administration. All rats that were irradiated at 100 J/cm 3 hours after PAD-S31 administration showed more than 50% tumor destruction. When the light dose was more than 150 J/cm, more than half of the rats showed complete tumor eradication, of which the average size was 6 mm., Conclusions: We report that PDT using PAD-S31 is effective for destroying bladder tumors in an orthotopic rat model. These experimental results suggest that this therapy could be a clinically promising method for the treatment of patients with bladder cancer.

Recent advances in molecular biology suggest that neuronal nicotinic acetylcholine receptors play important roles in the central nervous system (CNS). Of these receptors, the alpha7 group has recently attracted interest for its CNS-related actions and is looked to as a potential new class of pharmacological targets for cognition, schizophrenia, sensory gating, and anxiety. In the course of a research program aimed at the discovery of alpha7 receptor agonists with high affinity, subtype selectivity, and good pharmacokinetic profile, we discovered (R)-3'-(5-chlorothiophen-2-yl)spiro-1-azabicyclo[2.2.2]octane-3,5'-[1',3']oxazolidin-2'-one (25). Compound 25 has potent binding affinity (K(i) = 9 nmol/L) and good selectivity toward the other nicotinic subtypes (alpha4beta2 and alpha1beta2gammadelta) and has been found in pharmacokinetic evaluation to have good oral bioavailability and brain permeability.

All chlorophyll (Chl)-binding proteins involved in photosynthesis of higher plants are hydrophobic membrane proteins integrated into the thylakoids. However, a different category of Chl-binding proteins, the so-called water-soluble Chl proteins (WSCPs), was found in members of the Brassicaceae, Polygonaceae, Chenopodiaceae, and Amaranthaceae families. WSCPs from different plant species bind Chl a and Chl b in different ratios. Some members of the WSCP family are induced after drought and heat stress as well as leaf detachment. It has been proposed that this group of proteins might have a physiological function in the Chl degradation pathway. We demonstrate here that a protein that shared sequence homology to WSCPs accumulated in etiolated barley (Hordeum vulgare) seedlings exposed to light for 2 h. The novel 22-kD protein was attached to the outer envelope of barley etiochloroplasts, and import of the 27-kD precursor was light dependent and induced after feeding the isolated plastids the tetrapyrrole precursor 5-aminolevulinic acid. HPLC analyses and spectroscopic pigment measurements of acetone-extracted pigments showed that the 22-kD protein is complexed with chlorophyllide. We propose a novel role of WSCPs as pigment carriers operating during light-induced chloroplast development.

A case of haemangiopericytoma of right spermatic cord is reported. A 50-year old male presented with a month-lasting painless swelling of right scrotum. Ultrasonography revealed a soft tissue mass in right spermatic cord, which was about 3.5 cm in diameter. Right high inguinal orchiectomy was performed. The tumor was solid, smooth surfaced and well circumscribed. Histologically, the tumor had many capillary vessels and short spindle calls around the vessels. On the silver impregnation, argyrophil fibers surrounded the tumor cells. Immunohistologically, tumor cells were positive for CD34 antigen and negative for factor VIII antigen. The mitotic rate was 2 per highpower field. Accordingly, this tumor was diagnosed as benign haemangiopericytoma. The patient is doing well without any sign of recurrence, as of 30 months post-operatively. Haemangiopericytoma is a rare neoplasm of pericyte origin. It commonly occurs in retroperitoneum and lower extremities. To our knowledge, only two cases of malignant haemangiopericytoma of the spermatic cord was reported, and this case is the first benign case of the spermatic cord.

A case of synchronous triple carcinomas arising in the kidney, bladder and prostate is reported. An 82-year-old man had gross hematuria. Urine cytology was positive and intravenous pyelography showed right hydronephrosis with a filling defect in the bladder. Computed tomography revealed a 4 cm mass in the bladder, enlarged prostate and 6 cm renal mass at the left kidney. Cystoscopy demonstrated a papillary broadbased tumor with some small satellite tumors in the bladder, and magnetic resonance imaging revealed muscle invasion of the bladder tumor. This patient underwent left radical nephrectomy and total cystoprostatectomy with ileal conduit urinary diversion as radical treatment. Histological diagnosis was renal cell carcinoma, transitional cell carcinoma of the bladder. Furthermore, well-differentiated adenocarcinoma was found incidentally in the prostate. Immunohistochemical staining with anti-p53 antibody for the three tumors showed positive staining only for the bladder cancer.

Chronic allograft nephropathy (CAN) is due to both immunologic and non-immunologic factors and results in the development of nonspecific pathologic features that may even be present in long-term well-functioning renal allografts. To investigate the natural history of CAN and potential risk factors associated with progression of these histologic lesions, this study evaluated the of histologic alterations of 124 sequential protocol biopsies performed at 2, 3, and 5 yr after transplantation in 46 patients who exhibited histologic evidence of CAN in the 1-yr biopsy. The occurrence of late acute rejection (AR) greater than 4 mo posttransplant was significantly associated with the development of histologic CAN. In contrast, early clinical AR occurring within 3 mo had no impact on the subsequent development of CAN at 1 yr. Subclinical AR was evident in association with CAN in 50%, 32%, 19%, and 16% of cases with CAN at 1, 2, 3, and 5 yr, respectively. These acute lesions correlated significantly with histologic progression defined as an increased CADI score of the follow-up biopsies. Furthermore, a group of patients who exhibited repeated subclinical AR in the sequential follow-up biopsies had a lower creatinine clearance at 5 yr after transplantation and worse long-term graft survival. In contrast, the absence of evidence of acute inflammation in association with CAN at any time point was associated with minimal deterioration in renal function or progression of renal lesions during the observation period. These results suggest that the persistence of chronic active inflammation may be responsible for the histologic progression of CAN.

To determine the cause of the predilection of Babesia gibsoni for reticulocytes, the parasites were cultivated with various types of reconstituted erythrocyte ghosts, which were prepared by resealing erythrocyte ghosts together with variously treated erythrocyte lysate, in vitro. The level of parasitemia in the culture with reconstituted reticulocyte ghosts containing untreated reticulocyte lysate was significantly higher than that in the culture with reconstituted normocyte (mature erythrocyte) ghosts containing untreated normocyte lysate. The removal of mitochondria from reconstituted reticulocyte ghosts by filtration or centrifugation resulted in decreased of parasitemia in those cultures. In contrast, when mitochondria from reticulocytes were loaded into reconstituted normocyte ghosts, the parasitemia in the ghosts loaded mitochondria was increased to the same level as that in reconstituted reticulocyte ghosts. Furthermore, the parsitemia in the culture with reconstituted normocyte ghosts was proportional to the concentration of adenosine 5'-triphosphate in the ghosts. These results suggested that mitochondria of reticulocytes might enhance the multiplication of B. gibsoni through the generation of adenosine 5'-triphosphate within the cells.