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There is no uniform agreement on how to manage the unilateral nonfunctioning or poorly functioning kidney associated with posterior urethral valves. We studied the results of treatment of our patients to make recommendations regarding management of these kidneys.We reviewed the records of 13 boys with a history of posterior urethral valves and a unilateral nonfunctioning or poorly functioning kidney, defined as less than 10% of total renal function on 99mtechnetium dimercapto-succinic acid renal scans. Variables investigated included pyelonephritis, hypertension, vesicoureteral reflux, nephroureterectomy, ureteral reimplantation and spontaneous cessation of reflux. We also evaluated how the management of abnormal urodynamic parameters influenced the results of reimplantation or medically induced cessation of reflux.Three of the 6 boys with grade 5 reflux ipsilateral to the poorly functioning kidney required nephroureterectomy at a mean age of 21 months because of recurrent urinary tract infections. Another 4 boys underwent successful ureteral reimplantation, including 2 who had bilateral grade 5 reflux, and 2 who had ipsilateral grade 4 reflux, and grade 3 (1) and grade 2 (1) contralateral reflux. Of 4 boys ipsilateral grade 3 reflux in 3 and bilateral grade 5 reflux in 1 disappeared without surgery after treatment of urodynamic abnormalities. Two patients with poorly functioning kidneys and no reflux did not undergo surgery. Overall 10 of the 13 poorly functioning renal units were not removed, and these patients were free of pyelonephritis and hypertension. Ureteral reimplantation (4 ipsilateral and 3 contralateral) was performed only after urodynamic abnormalities were addressed. All reimplantations were successful.Based on our results we believed that unilateral poorly functioning kidneys in patients with posterior urethral valves can be safely preserved in select patients without hypertension and pyelonephritis. Reimplantation to correct reflux may be preferable to nephroureterectomy in specific situations, such as when contralateral function is suboptimal and the contralateral ureter needs reimplantation. When indicated, reimplantation can be performed successfully if abnormal urodynamic parameters are addressed preoperatively. In fact, treating abnormal urodynamic findings may lead to spontaneous reflux resolution.

The interstrand N2,N2-dG DNA cross-linking chemistry of the acrolein-derived gamma-OH-1,N2-propanodeoxyguanosine (gamma-OH-PdG) adduct in the 5'-CpG-3' sequence was monitored within a dodecamer duplex by NMR spectroscopy, in situ, using a series of site-specific 13C- and 15N-edited experiments. At equilibrium 40% of the DNA was cross-linked, with the carbinolamine form of the cross-link predominating. The cross-link existed in equilibrium with the non-crosslinked N2-(3-oxo-propyl)-dG aldehyde and its geminal diol hydrate. The ratio of aldehyde/diol increased at higher temperatures. The 1,N2-dG cyclic adduct was not detected. Molecular modeling suggested that the carbinolamine linkage should be capable of maintaining Watson-Crick hydrogen bonding at both of the tandem C x G base pairs. In contrast, dehydration of the carbinolamine cross-link to an imine (Schiff base) cross-link, or cyclization of the latter to form a pyrimidopurinone cross-link, was predicted to require disruption of Watson-Crick hydrogen bonding at one or both of the tandem cross-linked C x G base pairs. When the gamma-OH-PdG adduct contained within the 5'-CpG-3' sequence was instead annealed into duplex DNA opposite T, a mixture of the 1,N2-dG cyclic adduct, the aldehyde, and the diol, but no cross-link, was observed. With this mismatched duplex, reaction with the tetrapeptide KWKK formed DNA-peptide cross-links efficiently. When annealed opposite dA, gamma-OH-PdG remained as the 1,N2-dG cyclic adduct although transient epimerization was detected by trapping with the peptide KWKK. The results provide a rationale for the stability of interstrand cross-links formed by acrolein and perhaps other alpha,beta-unsaturated aldehydes. These sequence-specific carbinolamine cross-links are anticipated to interfere with DNA replication and contribute to acrolein-mediated genotoxicity.

Because alpha-tocopherol (alpha-TOH) mediates the peroxidation of cholesterol-esterified lipids in human low-density lipoprotein (LDL) in vitro and has displayed disappointing results against the onset and development of atherosclerosis, it may not be appropriate for use as a therapeutic in the prevention and/or treatment of the disease. Herein are described the experimental results demonstrating that 3-pyridinols spare alpha-TOH, do not efficiently mediate lipid peroxidation, and protect lipoprotein tryptophan residues in human LDL.

The model‐based inversion tools for eddy current signals have been developed by the novel combination of neural networks and finite element modeling for quantitative flaw characterization in steam generator tubes. In the present work, interpretation of experimental eddy current signals was carried out in order to validate the developed inversion tools. A database was constructed using the synthetic flaw signals generated by the finite element modeling. The hybrid neural networks of a PNN classifier and BPNN size estimators were trained using the synthetic signals. Experimental eddy current signals were obtained from axisymmetric artificial flaws. Interpretations of flaws were carried out by feeding experimental signals into the neural networks. The results of interpretations were excellent, so that the developed inversion tools would be applicable to the interpretation of experimental eddy current signals.

The identification of flaw signals in ultrasonic testing of welded joints is quite often very difficult in the angle beam testing of welded joints due to the presence of geometric reflectors, such as weld roots and counter bores, generating non-relevant signals. This paper describes a new approach to perform the flaw identification in such a problematic situation. This approach involves four steps: 1) acquisition of “reference” signals for both flaws and geometric reflectors, 2) normalizing both reference signals and testing signals, 3) deconvolution of angle beam testing signals by references, and 4) discrimination of flaw signals from geometric reflections by means of the patterns of deconvolution results. As results, proposed technique has a great potential to identify similar signal, especially to distinguish notch signals from the geometric reflections. The similarity function has narrow width in time domain, and could improve accuracy in time of flight.

The subject of this article is a patient with sarcoidosis with neurological involvement, who failed to respond to high dose steroid therapy and cyclophosphamide. Low doses (20 Gy) of total nodal and craniospinal irradiation resulted in an excellent response, the patient being alive and in good health 3 years after irradiation without any further steroid therapy.

The solution structure of the (-)-(1R,2S,3R,4S)-N6-[1-(1,2,3, 4-tetrahydroxy-benz[a]anthracenyl)]-2'-deoxyadenosyl adduct at X6 of 5'-d(CGGACXAGAAG)-3'.5'-d(CTTCTTGTCCG)-3', incorporating codons 60, 61(italic), and 62 of the human N-ras protooncogene, was determined. This adduct results from the trans opening of 1S,2R,3R,4S-1, 2-epoxy-1,2,3,4-tetrahydro-benz[a]anthracenyl-3,4-diol by the exocyclic N6 of adenine. Molecular dynamics simulations were restrained by 509 NOEs from 1H NMR. The precision of the refined structures was monitored by pairwise root-mean-square deviations which were1.2 A; accuracy was measured by complete relaxation matrix calculations, which yielded a sixth root R factor of 9.1 x 10(-)2 at 250 ms. The refined structure was a right-handed duplex, in which the benz[a]anthracene moiety intercalated from the major groove between C5.G18 and R,S,R,SA6.T17. In this orientation, the saturated ring of BA was oriented in the major groove of the duplex, with the aromatic rings inserted into the duplex such that the terminal ring of BA threaded the duplex and faced toward the minor groove direction. The duplex suffered localized distortion at and immediately adjacent to the adduct site, evidenced by the increased rise of 8.8 A as compared to the value of 3.5 A normally observed for B-DNA between base pairs C5.G18 and R,S,R,SA6.T17. These two base pairs also buckled in opposite directions away from the intercalated BA moiety. The refined structure was similar to the (-)-(7S,8R,9S,10R)-N6-[10-(7,8,9, 10)-tetrahydrobenzo[a]pyrenyl)]-2'-deoxyadenosyl adduct of corresponding stereochemistry at X6 of the same oligodeoxynucleotide [Zegar, I. S., Kim, S. J., Johansen, T. N., Horton, P. J., Harris, C. M., Harris, T. M., and Stone, M. P. (1996) Biochemistry 35, 6212-6224]. Both adducts intercalated toward the 5'-direction from the site of adduction. The similarities in solution structures were reflected in similar biological responses, when repair-deficient AB2480 Escherichia coli were transformed with M13mp7L2 DNA site-specifically modified with these two adducts.

4-1BB (CD137) regarded as a powerful T-cell costimulatory molecule. However, recent studies indicate that in vivo 4-1BB stimulation is able to actively suppress the antigen-specific immune response by inducing indoleamine 2,3-dioxygenase (IDO) in antigen-presenting cells. Since we found that both 4-1BB and IDO were induced in the placenta during pregnancy, we questioned whether 4-1BB signaling would be negative or positive on the pregnancy. By treating agonistic anti-4-1BB mAb or blocking anti-4-1BBL mAb to the pregnant mice, we tested the role of 4-1BB. Treatment of agonistic anti-4-1BB mAb markedly increased the abortion of allogeneic fetus, which was primarily dependent on the CD8+ T cells. Since anti-4-1BB treatment induced the accumulation of C3 component in the placenta, which was reversed by treating depleting anti-CD8 mAb, C3 complement seemed to be functioned as an effector molecule in the placenta. However, blockade of 4-1BB / 4-1BBL interaction or 4-1BB stimulation to the syngeneic fetus showed a marginal effect on the pregnancy. These results indicate that 4-1BB signal may be involved in the regulation of immune responses between maternal T cells and fetal tissues. This study was supported by the Science Research Center Fund from KOSEF and the Korean Ministry of Science and Technology.

Transurethral resection of the external sphincter in patients with spinal cord injury and detrusor-external sphincter dyssynergia has high failure and reoperation rates. Retrospectively we examined elevated bladder leak point pressure after transurethral resection of the external sphincter as an indicator of failure.A total of 55 spinal cord injury patients (mean age 50 years) underwent 1 or more sphincter resections, most recently a mean of 11 years ago. We reviewed the most recent urodynamic studies for bladder leak point pressure, bladder compliance and persisting external detrusor-sphincter dyssynergia. Each patient was assessed for the presence of an indwelling catheter, upper tract damage, stones, bacteriuria, autonomic dysreflexia and vesicoureteral reflux. The incidence of each of these urodynamic and clinical parameters among patients with bladder leak point pressure less than 40 cm. water was compared to the incidence among those with bladder leak point pressure greater than 40 cm. water.Patients with bladder leak point pressure greater than 40 cm. water had a significantly higher incidence of upper tract damage (p = 0.021) and persisting external detrusor-sphincter dyssynergia (p = 0.00008). The incidence of an indwelling catheter was no different between patients with bladder leak point pressure less than and greater than 40 cm. water.Bladder leak point pressure greater than 40 cm. water is a valid indicator of failure of transurethral resection of the external sphincter since there is a significantly higher incidence of upper tract damage and persisting external detrusor-sphincter dyssynergia in these patients. Patients with favorable urodynamic parameters after transurethral resection of the external sphincter but with indwelling catheters were poorly selected for this procedure. Furthermore, those without an indwelling catheter after transurethral resection of the external sphincter may still have adverse urodynamic parameters and are at significant risk for upper tract damage.

This chapter presents the application of quadratic optimization for motion control to feedback control of robotic systems using Cerebellar Model Arithmetic Computer (CMAC) neural networks. Explicit solutions to the Hamilton-Jacobi-Bellman (H-J-B) equation for optimal control of robotic systems are found by solving an algebraic Riccati equation. It is shown how CMAC can cope with nonlinearities through optimization with no preliminary off-line learning phase required. The adaptive learning algorithm is derived from Lyapunov stability analysis, so that both system tracking stability and error convergence can be guaranteed in the closed-loop system. The filtered tracking error or critic gain and the Lyapunov function for the nonlinear analysis are derived from the user input in terms of a specified quadratic performance index. Simulation results on a two-link robot manipulator show the satisfactory performance of the proposed control schemes even in the presence of large modeling uncertainties and external disturbances.

The long-term benefits of oral oxybutynin in spinal cord injured patients with indwelling catheters is unknown. We reviewed our experience with this population of men and present the results of our analysis.A total of 109 male spinal cord injured patients at the Houston Veterans Affairs Medical Center have been treated with chronic indwelling catheters (80 transurethral and 29 suprapubic). Thirty-eight patients (35%) were identified as using oxybutynin on a regular basis. These patients were compared to those not using oxybutynin with regard to urodynamic parameters and upper tract deterioration. Specifically examined were bladder compliance, bladder leak point pressure, vesicoureteral reflux, hydronephrosis, urolithiasis, febrile urinary tract infections and serum creatinine greater than 2 mg./dl.The mean duration of indwelling catheter use was 11.9 years (12.4 without oxybutynin and 10.9 on oral oxybutynin). Of the 31 patients with normal compliance (greater than 20 ml./cm. water), 24 (77%) were using oxybutynin (p = 0.001). Bladder leak point pressures were abnormal (greater than 35 cm. water) in 5 of 32 patients (16%) on oxybutynin versus 34 of 60 (57%) without it (p0.001). Hydronephrosis was present in 15 of 66 patients (23%) without oxybutynin versus 1 of 36 (3%) with oxybutynin (p = 0.009). Febrile urinary tract infections occurred in 4 of 35 patients (11%) versus 17 of 62 patients (27%) with or without oxybutynin, respectively (p = 0.077). No significant differences were found between the 2 groups with regard to reflux, renal scars, stones or elevated serum creatinine.It appears that regular use of oxybutynin may be beneficial in spinal cord injured patients who require chronic indwelling catheters for bladder management. Our analysis reveals that patients who take oxybutynin regularly have better bladder compliance, lower bladder leak point pressures and less hydronephrosis. Until a prospective, randomized trial reveals contradicting outcomes, empiric use of oxybutynin in all spinal cord injured patients requiring chronic indwelling catheters seems justified.

Abnormal urodynamic findings are common in boys with a history of posterior urethral valves. However, to our knowledge there are few reports on the results of treating these abnormal findings. We analyzed the treatment of abnormal urodynamic parameters and its outcome in 21 boys who underwent valve ablation.After valve ablation multichannel urodynamic studies were performed in 31 boys, including 21 in whom studies were done before and after therapy was started for abnormal parameters. Detrusor instability and impaired bladder compliance were treated with anticholinergics or augmentation cystoplasty, and impaired detrusor contractility was managed with clean intermittent catheterization.Before therapy 17 of 21 boys had impaired compliance and detrusor instability, 2 had impaired compliance without instability and 2 had instability alone. After treatment 8 boys had impaired compliance and 4 had detrusor instability. After anticholinergics were initiated new onset myogenic failure in 2 boys necessitated clean intermittent catheterization. Of the 13 patients who presented with urinary incontinence 10 became dry and 3 had improvement with therapy. Vesicoureteral reflux in 10 boys at the time of the initial urodynamic study resolved in 7 with anticholinergic medication and in 1 after clean intermittent catheterization was begun for severely impaired compliance. All 21 boys were treated with anticholinergics and 2 were ultimately treated with augmentation cystoplasty. Clean intermittent catheterization was also instituted in 5 patients, including the 2 who required clean intermittent catheterization after myogenic failure developed. Five boys with high voiding pressures were found to have outlet obstruction due to residual valve tissue in 2, bladder neck obstruction in 2 and urethral stricture in 1 despite normal flow rates in 2.Urodynamic studies are helpful in guiding therapy in boys after valve ablation. Anticholinergic therapy can improve compliance, decrease detrusor instability, improve continence and eliminate vesicoureteral reflux in the majority of boys, although there is an associated risk of myogenic failure. Flow rates and fluoroscopic voiding studies are often unable to detect outlet obstruction and must be obtained in conjunction with voiding pressure measurements to make this diagnosis.

Using mechanical and chemical dissection methods, fibrous sheath was isolated both from normal ejaculated human spermatozoa and from rabbit cauda epididymal spermatozoa. The same techniques did not produce a pure preparation of fibrous sheath from ejaculated rabbit spermatozoa, suggesting that further cross-linking and stabilization of sperm structures occurs in response to components of the seminal plasma. The isolation procedures were monitored by phase contrast microscopy and the purity of the fibrous sheath was verified by electron microscopy. Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) of isolated human fibrous sheath revealed at least 14 protein bands of which the most intensely stained were of molecular weight 84, 72, 66.2, 57, 32 and 28.5 kDa. The rabbit fibrous sheath revealed at least 10 protein bands, of which the most intensely stained were 35.2, 32.7 and 28.5 kDa. The amino acid composition of the purified fibrous sheath from human and rabbit spermatozoa was similar, being high in aspartic acid and/or asparagine and glutamic acid and/or glutamine, serine, alanine, leucine, lysine and glycine, but low in histidine, tyrosine and isoleucine. This composition is similar to that reported for the rat and suggests that mammalian sperm tail fibrous sheaths are composed of similar types of proteins, although there are apparent differences in protein components between species.

Longitudinal and shear waves are the fundamental elastic wave modes in an infinite unbounded solid and their velocities are determined by the mass density and elastic moduli of propagationg medium. Thus, elastic moduli could be determined by measuring the phase velocities of longitudinal and shear waves using the corresponding mode transducers.

Acoustic impedance mismatch at the fluid-wall interface was shown to affect the spectra from an intravascular Doppler device in an in vitro model with a diameter typical of human coronary arteries. Measurements were obtained first under Poiseuille flow conditions with impedance mismatches of 0%, 7% and 12%, and then under stenosed conditions for the 0% and 7% mismatch cases. For the zero mismatch case, the Doppler spectra could be readily interpreted in terms of fluid mechanical phenomena. When mismatch was present, the spectra from Poiseuille flow exhibited multiple peaks which could not be directly related to the velocity profile. Also, the spectra from stenosed flow with a mismatch of 7% were similar to those from the zero mismatch case but did not exhibit the specific flow-related features as clearly. These results indicate that the impedance mismatch alters the acoustic environment inside the model and that this causes artifact in the Doppler spectra.

Polycyclic aromatic hydrocarbons are metabolized to a wide variety of oxidized derivatives, including highly reactive diol epoxides which alkylate DNA. The reaction lacks regio- or stereospecificity but occurs primarily at the exocyclic amino groups of deoxyguanosine and deoxyadenosine. An efficient route to N 6 adducts of deoxyadenosine is described using as examples those arising from trans opening of the anti -tetrahydrodiol epoxides of naphthalene, benzo[ a ]pyrene, and benzo[ c ]phenanthrene. The adducts were synthesized in 50–92% yields by reaction of 6-fluoropurine 2′-deoxyriboside with aminotriols formed by trans opening of racemic dihydrodiol epoxides using liquid NH 3 . The diastereomeric adducts were separated by HPLC and their absolute configurations were assigned by circular dichroism. 1 H NMR studies revealed significant differences in conformation of the tetrahydroaromatic ring between the sterically unrestricted naphthalene derivative and the sterically congested derivatives of benzo[ a ]pyrene and benzo[ c ]phenanthrene. These differences may have a bearing on the higher carcinogenicity shown by the latter hydrocarbons. Undecadeoxyoligonucleotides bearing regio- and stereochemically defined adenine N 6 - anti - trans -benzo[ a ]pyrene adducts have been prepared.

Spectroscopic evidence is presented for the formation of a carbinolamine interchain cross-link in 5'-CpG-3' sequences, arising from the acrolein adduct gamma-OH-PdG. This may be important in understanding biological processing of acrolein-induced DNA damage in CpG sequences.

4-1BB(CD137) is a member of the tumor necrosis factor receptor superfamily and is expressed on avtivated T cells, monocytes and natural killer (NK) cells. The expression of 4-1BB has been known to be activation dependent except regulatory T cells. Interestingly, we found that 4-1BB has three promoter regions which could regulate 4-1BB mRNA level. Thus, we investigated expression level of three different transcripts of 4-1BB in naïve T cells and EL4 cell lines. It was reported that 4-1BB expresson was increased by several anti-cancer drugs in human peripheral blood mononuclear cells and CEM cells. We also test whether the treatment with anti-cancer drugs could induce 4-1BB expression in naïve T cells and EL4 cells. The data indicated that 4-1BB expression increased by agents such as mitomycin C, 5-FU, and doxorubicin. Especially, type II transcript of 4-1BB was preferentially induced in naïve T cells stimulated by anti-CD3 because of NFkB binding site in type II promoter region. It suggests that type II promoter region is major promoter which could be activated in naïve T cells by TCR signaling. We also found a splicing variant deleted exon 7 including transmembrane domain region could inhibit the 4-1BB signaling. Our studies demonstrated that 4-1BB has three promoter could induce the expression of 4-1BB mRNA but the type II promoter is a inducible promoter in naïve T cell and costimulatory effect through 4-1BB receptor could be modulated by soluble 4-1BB produced by splicing variant without transmembrane domain induced in activation of naïve T cells.

The living cationic polymerization mechanism is considered in view of the classical coludysis mechanism. In is proposed that, in the case of vinyl ether polymerization via a halogenated acetic acid ester in hexane, a fully ionic intermediate may not be necessary for the polymerization

A retrospective analysis of 61 patients with Stage II carcinoma of the endometrium was carried out. Our results suggest that when given carefully and adequately, radiation therapy alone is as effective as a combination of surgery and irradiation and is well tolerated. Five-year actuarial survival was 74.5% in patients treated with radiation therapy alone (16 patients) as compared to those patients who received either preoperative radiation (35 patients) or postoperation radiation (ten patients) where the survival was 70.8% and 78.3%, respectively (P greater than or equal to 0.05). Tumor was controlled in the pelvis in 93.4% of patients. Complications of treatment were seen in 8.2%. With the exception of one patient with bowel obstruction requiring surgery, the rest of the complications were minor. From these results, it appears that a planned radiotherapy is a good alternative to combination of surgery and irradiation.

Clinically significant spinal implants develop in intracranial ependymomas. Spinal subarachnoid implants developed in 11 of 32 patients who received local irradiation at the University of Michigan between 1955 and 1972 for intracranial ependymoma. Seven of these patients received spinal axis irradiation for neurological disturbances resulting from the implants, and implants were found in the other 4 patients postmortem. Ten patients had infratentorial tumors, and one had a supratentorial tumor; nine tumors were poorly differentiated, two were well differentiated. The authors conclude that spinal irradiation is required if the tumor is poorly differentiated, or located in the infratentorial fossa.

Rat outer dense fibres were isolated from cauda epididymal spermatozoa using mechanical and chemical dissection methods. Sperm tail isolation procedures were monitored by phase-contrast microscopy and the purity of the outer dense fibres was verified by electron microscopy. SDS-PAGE of isolated outer dense fibres revealed at least nine Coomassie brilliant blue stained bands, and 12 silver staining bands. The most abundant proteins were a large band between 26.5 and 32.5 kDa, and 84 kDa, 21.5 kDa and 15.5 kDa bands. The amino acid composition of the total rat outer dense fibres and seven isolated proteins showed similar compositions, being abundant in aspartic and glutamic acid, serine, glycine and leucine. However, the content of cysteine and proline was highly variable among the isolated proteins. Immunofluorescence microscopy demonstrated that a polyclonal antiserum to isolated rat outer dense fibres showed positive staining localized to the mid-piece of rat and rabbit spermatozoa. However, there was crossreactivity in the principal piece as well as the mid-piece of the human spermatozoa. The antiserum also showed crossreactivity in the perforatorium of rat sperm heads and the acrosome and equatorial segment of rabbit sperm heads. These data indicate that it is technically possible to isolate proteins from the outer dense fibres that will enable further studies of the amino acid sequences of sperm tail proteins.