Transurethral cystotomy repair.
We present a novel transurethral technique for cystotomy repair. This method can be used for immediate bladder repair following limited bladder injury and avoids the morbidity associated with laparotomy.
Humans↗
Biomedical subjects
M Gupta
Publications and source records attributed to M Gupta.
Crossing vessels. Endourologic implications.
The controversy regarding the functional significance of vessels crossing at the ureteropelvic junction is not a new one, though this debate has been resurrected in recent years because of application of endourologic techniques to manage ureteropelvic junction (UPJ) obstruction. The principle limitation of endoscopic treatment of UPJ obstruction is the inferior success rate compared to open dismembered pyeloplasty. The influence crossing vessels may have in affecting both the success rates and complications of endoscopic treatment of UPJ obstruction has yet to be resolved. Crossing vessels may be important for two reasons: (1) they are a potential source of hemorrhage following endoscopic incision, and (2) they may play an etiologic role in UPJ obstruction and therefore may be a reason for failure of endoscopic techniques. This article reviews some of the historical aspects of crossing vessels and explores recent studies that are starting to shed some light on this controversial topic.
Humans↗
Estrogenic and antiestrogenic activities of 16alpha- and 2-hydroxy metabolites of 17beta-estradiol in MCF-7 and T47D human breast cancer cells.
The comparative mitogenic activities of 17beta-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 2-hydroxyestrone (2-OHE1), 16alpha-hydroxyestradiol (16alpha-OHE2) and 16alpha-hydroxyestrone (16alpha-OHE1) were determined in estrogen receptor (ER)-positive MCF-7 and T47D human breast cancer cells. E2 (1 nM) induced a 7- to 13-fold increase in cell number in both cell lines compared to untreated cells and the mitogenic potencies of 16alpha-OHE1 or 16alpha-OHE2 were comparable to or greater than E2. In contrast, 2-OHE1 and 2-OHE2 were weak mitogens in both cell lines and in cells cotreated with 1 nM E2 and 100 or 1000 nM 2-OHE1 or 2-OHE2, there was a significant inhibition of hormone-induced cell proliferation. The comparative ER agonist/antagonist activities of E2 and the metabolites on transactivation were determined in T47D cells transiently transfected with constructs containing promoter inserts from the cathepsin D (pCD) and creatine kinase B (pCKB) genes. E2, 16alpha-OHE2 and 16alpha-OHE1 induced reporter gene activity in both MCF-7 or T47D cells transfected with pCKB or pCD. In contrast, 2-OHE1 and 2-OHE2 did not exhibit ER agonist activity for these transactivation assays, but in cells cotreated with E2 plus 2-OHE1 or 2-OHE2, there was a significant decrease in the hormone-induced response. These results demonstrate that 16alpha-OHE1/16alpha-OHE2 exhibit estrogenic activities similar to that observed for E2, whereas the 2-catecholestrogens are weak ER agonists (cell proliferation) or antagonists (cell proliferation and transactivation).
Breast Neoplasms↗
Induction of thyroiditis in mice with thyrotropin receptor lacking serologically dominant regions.
Grave's disease (GD) is characterized by pathogenic autoantibodies to the human thyrotropin receptor (hTSH-R), and is frequently associated with a lymphocytic infiltrate of the thyroid gland. In attempts to establish a murine model of GD, we and others have previously shown that immunization of mice with recombinant preparations of the hTSH-R ectodomain induces high titres of specific antibodies, which, however, are not pathogenic, nor is the response accompanied by the development of thyroiditis. Since earlier reports identified the serological immunodominant determinants within the N- and C-terminal regions of hTSH-R ectodomain, we reasoned that immunization of mice with truncated fragments of ectodomain lacking these dominant regions might result in skewing of the response to other determinants of the molecule, with consequent induction of immunopathological features present in GD. We show here that multiple challenge of BALB/c mice with an amino acid fragment of residues 43-282 generates antibodies directed at hTSH-R peptides 37-56, 157-176, 217-236 and 232-251. This reactivity pattern is distinct from that induced previously with the whole ectodomain of hTSH-R in BALB/c animals. Thyroid function remained unaffected in these mice, suggesting that pathogenic antibodies were not being induced. Interestingly, some animals developed lymphocytic infiltration of the thyroid gland, clearly indicating the presence of pathogenic T cell determinants within the 43-282 fragment. Challenge with the related fragment 43-316 produced the same pattern of serological response to the synthetic peptides as fragment 43 282, but was not accompanied by thyroiditis. The results demonstrate: (i) the presence of thyroiditogenic determinants within hTSH-R, and (ii) that these pathogenic determinants are likely to be cryptic, as their effect is exhibited only when the hierarchy of immunodominance within hTSH-R is drastically altered.
Animals↗
Imagery and hypnotizability revisited.
The objective of this study was to correlate computer-generated imagery tasks and a self-report measure of imagery ability with hypnotizability, hypothesizing that computer-generated imagery tasks would be better predictors of hypnotizability than will the self-report measure. Hypnotizability of 43 subjects was assessed using the Hypnotic Induction Profile and the Stanford Hypnotic Susceptibility Scale, Form C. Imagery ability was assessed by the Visual Vividness Imagery Questionnaire (VVIQ) and by computer-generated imagery tasks measuring the ability to generate, maintain, and transform images. Although there was no correlation between the VVIQ and hypnotizability, the less hypnotizable subjects made twice as many mistakes in the spatial imagery tasks than did the more hypnotizables, but this difference was not statistically significant. The relationships among hypnotic performance, hypnotizability, and imagery functions are complex.
Adolescent↗
Tissue-restricted expression of the cardiac alpha-myosin heavy chain gene is controlled by a downstream repressor element containing a palindrome of two ets-binding sites.
The expression of the alpha-myosin heavy chain (MHC) gene is restricted primarily to cardiac myocytes. To date, several positive regulatory elements and their binding factors involved in alpha-MHC gene regulation have been identified; however, the mechanism restricting the expression of this gene to cardiac myocytes has yet to be elucidated. In this study, we have identified by using sequential deletion mutants of the rat cardiac alpha-MHC gene a 30-bp purine-rich negative regulatory (PNR) element located in the first intronic region that appeared to be essential for the tissue-specific expression of the alpha-MHC gene. Removal of this element alone elevated (20- to 30-fold) the expression of the alpha-MHC gene in cardiac myocyte cultures and in heart muscle directly injected with plasmid DNA. Surprisingly, this deletion also allowed a significant expression of the alpha-MHC gene in HeLa and other nonmuscle cells, where it is normally inactive. The PNR element required upstream sequences of the alpha-MHC gene for negative gene regulation. By DNase I footprint analysis of the PNR element, a palindrome of two high-affinity Ets-binding sites (CTTCCCTGGAAG) was identified. Furthermore, by analyses of site-specific base-pair mutation, mobility gel shift competition, and UV cross-linking, two different Ets-like proteins from cardiac and HeLa cell nuclear extracts were found to bind to the PNR motif. Moreover, the activity of the PNR-binding factor was found to be increased two- to threefold in adult rat hearts subjected to pressure overload hypertrophy, where the alpha-MHC gene is usually suppressed. These data demonstrate that the PNR element plays a dual role, both downregulating the expression of the alpha-MHC gene in cardiac myocytes and silencing the muscle gene activity in nonmuscle cells. Similar palindromic Ets-binding motifs are found conserved in the alpha-MHC genes from different species and in other cardiac myocyte-restricted genes. These results are the first to reveal a role of the Ets class of proteins in controlling the tissue-specific expression of a cardiac muscle gene.
Animals↗
Inhibition of vascular and epithelial differentiation in murine nitrofen-induced diaphragmatic hernia.
Neonates with congenital diaphragmatic hernia (DH) die of pulmonary hypoplasia and persistent pulmonary hypertension. We used immunohistochemical localization of alpha-smooth muscle actin (alpha-SMA), platelet endothelial cell adhesion molecule (PECAM)-1, thyroid transcription factor (TTF)-1, surfactant protein (SP) A, SP-C, and competitive RT-PCR quantitation of TTF-1, SP-A, SP-C, and alpha-SMA mRNA expression to characterize the epithelial and vascular phenotype of lungs from ICR fetal mice with a nitrofen-induced DH. Nitrofen (25 mg) was gavage fed to pregnant mice on day 8 of gestation. Fetal mice were delivered on day 17. The diaphragm was examined for a defect, and the lungs were either fixed, sectioned, and immunostained or processed for mRNA isolation. In comparison with control lungs, DH lungs showed increased expression of alpha-SMA mRNA, fewer and more muscular arterioles (alpha-SMA), less well-developed capillary networks (PECAM-1), delayed epithelial development marked by a persistence of TTF-1 in the periphery, and decreased SP-A mRNA and SP-A expression. These data suggest that in the murine nitrofen-induced DH, as in human congenital DH, pulmonary insufficiency is due to an inhibition of peripheral pulmonary development including terminal airway and vascular morphogenesis.
Actins↗
Phase I/II trial of all-trans retinoic acid and tamoxifen in patients with advanced breast cancer.
Because tamoxifen and all-trans-retinoic acid (ATRA) have additive antitumor effects in preclinical systems, we performed a Phase I/II clinical trial of this combination in patients with advanced breast cancer. Patients with potentially hormone-responsive advanced breast cancer were enrolled. All received 20 mg of tamoxifen by mouth daily. Consecutive cohorts of 3-6 patients were treated on odd-numbered weeks with ATRA at doses of 70, 110, 150, 190, or 230 mg/m2/day. Twenty-six patients were entered in this trial; 25 were evaluable. A dose of 230 mg/m2 ATRA produced unacceptable headache and dermatological toxicity, but doses < or = 190 mg/m2 were tolerable. Two of 7 patients with measurable disease responded. Seven of 18 patients with evaluable, nonmeasurable disease achieved disease stability for more than 6 months. Plasma AUCs on day 1 of successive weeks of treatment were stable over time. A nonsignificant decrease in serum insulin-like growth factor I levels was noted during treatment, but this trend was similar to that observed in three "control" patients treated with tamoxifen alone. When given with daily tamoxifen, the maximum tolerated dose of ATRA that could be given on alternate weeks was 190 mg/m2/day. This schedule of ATRA resulted in repeated periods of exposure to potentially therapeutic concentrations of ATRA. Declines in the serum insulin-like growth factor I concentrations observed in patients treated with tamoxifen and ATRA were similar to those observed in patients treated with tamoxifen alone. Objective responses were observed, some in patients who had previously progressed while receiving tamoxifen, suggesting that further studies would be of interest.
Adult↗
Effect of leaf extract from Clerodendron colebrookianum on CNS function in mice.
Effect of acute multiple (20, 40 and 80 mg/kg body wt, i.p.) doses of C. colebrookianum leaf extract on behaviour, convulsion, analgesia and sedative-hypnosis was studied in mice. A marginal reduction of awareness and motor activity was observed in low (20 mg) and moderate (40 mg) dose level of extract. However, 80 mg dose caused marked inhibition of awareness and motor activity. Grip strength and stereotypy was observed in all the dose levels. The extract alone did not show loss of righting reflex but it prolonged the effect of meprobamate, diazepam, chlorpromazine and pentobarbitone significantly in a dose dependent manner. The extract neither produced analgesia alone nor it altered analgesic effect of morphine and pethidine. Pretreatment of the extract caused significant protection of strychnine and leptazol induced convulsion and mortality. The results suggest a mild (or dose dependent) CNS depressant action of leaf extract of C. colebrookianum in mice.
Animals↗
Differential regulation of T cell activation for primary versus secondary proliferative responses.
T cell activation in vivo results in proliferation and generation of effector cytokine-secreting cells, as also in development of memory cells that mount enhanced responses upon restimulation. However, differences in the signals promoting generation of effector vs memory T cells are not yet characterized. In this study, using various strategies to modulate an allorecognition system for priming human T cells in vitro, we show that there are indeed differences between the signaling requirements for a first proliferative response and those for priming T cells for enhanced recall proliferative responses. Using APCs fixed with varying concentrations of paraformaldehyde, we show that the loss of ability of these APCs to generate a first response is not matched by a similar loss in their ability to prime responder T cells for recall responses. Prevention of DNA replication during T cell priming with aphidicolin, a DNA polymerase inhibitor, is not inimical to successful T cell priming. Thus, clonal expansion during priming is less crucial than the primed activation status of T cells for the enhanced recall response. We also show that pentoxifylline, a phosphodiesterase inhibitor, inhibits the primary proliferative response, but its presence during priming enhances the recall response capabilities of T cells. On the other hand, the presence of the calcineurin inhibitor cyclosporin A during priming reduces the efficiency of priming, but at low concentrations it induces, like pentoxifylline, enhancement in recall response capability. These findings have significant implications in designing immunosuppressive therapy and in the analysis of signals for T cell memory commitment.
Aphidicolin↗
Effects of uracil incorporation, DNA mismatches, and abasic sites on cleavage and religation activities of mammalian topoisomerase I.
Abasic sites and deamination of cytosine to uracil are probably the most common types of endogenous DNA damage. The effects of such lesions on DNA topoisomerase I (top1) activity were examined in oligonucleotides containing a unique top1 cleavage site. The presence of uracils and abasic sites within the first 4 bases immediately 5' to the cleavage site suppressed normal top1 cleavage and induced new top1 cleavage sites. Uracils immediately 3' to the cleavage site increased cleavage and produced a camptothecin mimicking effect. A mismatch with a bulge or abasic sites immediately 3' to the top1 cleavage site irreversibly trapped top1 cleavable complexes in the absence of camptothecin and produced a suicide cleavage complex. These results demonstrate that top1 activity is sensitive to physiological, environmental, and pharmacological DNA modifications and that top1 can act as a specific mismatch- and abasic site-nicking enzyme.
Animals↗
Rotational changes of the vertebral pelvic axis after sublaminar instrumentation in adolescent idiopathic scoliosis.
STUDY DESIGN: The authors studied the rotational effect of sublaminar wiring on the spinal pelvic axis on 20 patients who were being treated for adolescent idiopathic scoliosis. OBJECTIVES: To determine if sublaminar wiring effectively derotates the scoliotic spine. SUMMARY OF BACKGROUND DATA: The correction of the rotational deformity in adolescent scoliosis via sublaminar wiring is not well quantified in the literature. The derotation maneuver of Cotrel-Dubousset has been shown to produce variable and unpredictable amounts of axial derotation. METHODS: Twenty patients who underwent posterior spine fusion for adolescent idiopathic scoliosis were evaluated using computed tomography scans and plain radiography before and after surgery and at a subsequent follow-up examination (average time of follow-up examination, 35 months after surgery). The degree of angle of vertebral rotation about the sagittal plane and that relative to the pelvis were measured before and after surgery and at a follow-up examination. RESULTS: The primary thoracic curves were not derotated significantly relative to the pelvis with sublaminar wiring. Primary thoracolumbar curves instrumented on the convexity with pedicle screws were derotated significantly relative to the pelvis (P = .001). The average initial correction was 57%. On final follow-up examination, the correction was 24% (18 of 20 twenty individuals lost axial correction by an average of 34%). In nine of 20 patients the spine was more rotated, relative to the pelvis, than it had been before surgery. No coronal or sagittal decompensation was seen in any curve type. CONCLUSIONS: Coronal and sagittal plane correction of scoliotic curves may be achieved with sublaminar instrumentation. The ability to derotate axially the scoliotic spine appears to be variable, however, and, in most cases, curve-type dependent. Over time, much correction appears to be lost, and in many patients the scoliosis actually becomes worse than it was before surgery. Nonetheless, the apical derotation that takes place appears to be reasonably true: the percent correction of angle of rotation about the sagittal plane and the percent correction of angle of rotation about the sagittal plain relative to the pelvis were closely correlated. Derotation forces applied to the instrumented spine do not appear to be transmitted to more distal segments.
Adolescent↗
Expression of retinoid-responsive genes occurs in colorectal carcinoma-derived cells irrespective of the presence of resistance to all-trans retinoic acid.
BACKGROUND AND OBJECTIVES: Retinoids are metabolized in human intestinal epithelial cells to all-trans retinoic acid; however, it is unknown whether these cells express retinoid receptors, and whether sensitivity or resistance to the hormone is associated with a particular pattern of expression of retinoid-responsive genes. METHODS: Northern blot analysis and reverse transcriptase polymerase chain reaction (RT-PCR) were used to identify mRNAs for retinoid receptors. Both Relative RT-PCR and transfection of retinoid-inducible plasmid were applied to test functionality of the pathway in a model system for colorectal carcinoma progression (primary SW480, all-trans retinoic acid-sensitive cells vs. metastatic SW620, -insensitive cells). RESULTS: Three colorectal carcinoma-derived cell lines were inhibited by the hormone. Retinoic acid receptor type alpha (hRAR alpha) and retinoid X receptor type alpha (hRXR alpha) mRNAs were detected in normal enterocytes, colonocytes, and in all colorectal carcinoma-derived cells studied. Primary carcinomas and metastatic lesions expressed high amounts of hRAR alpha receptor protein, showing no simple correlation between the amounts of mRNA and receptor protein. No pattern of expression of the retinoid-responsive genes was associated with sensitivity or resistance to the retinoid. Expression of the genes occurred irrespective of resistance to the hormone or inactivity of the pathway. CONCLUSIONS: Colonocytes possess a molecular system for transduction of the retinoid signal. All-trans retinoic acid modifies gene expression and inhibits proliferation of these cells. Therefore, retinoids are likely to be effective in chemoprevention of colorectal carcinoma.
Antineoplastic Agents↗
Oxidative stress induced by iron in Hydrilla verticillata (l.f.) Royle: response of antioxidants.
The effect of iron (FeCl3) on chlorophyll content, lipid peroxidation product, potassium ion leakage (a measure of damage to the permeability barrier), and antioxidants was studied in Hydrilla verticillata. The effect of iron-induced damage to the plant was compared with those of N-ethyl maleimide (NEM), a sulfhydryl reagent, and cumene hydroperoxide (CHP), an organic peroxide known to induce lipid peroxidation by free radical formation. The level of lipid peroxidation product was increased in the plants treated with Fe, CHP, and CHP + NEM but not with NEM alone. A significant increase in potassium ion leakage to the external solution was observed by the addition of Fe, CHP, and CHP + NEM, while this did not increase significantly in NEM-treated plants. When NEM and CHP were added simultaneously, the results were the same as those obtained with high iron concentrations, suggesting a combined effect of thiol depletion and lipid peroxidation by Fe ions. In addition, the results indicated loss of glutathione (GSH) and increased oxidized glutathione (GSSG) under Fe stress, indicative of oxidative stress. The oxidative stress may increase the production of free radicals and subsequently resulted in peroxidation of lipids. Further, addition of iron increased the activity of superoxide dismutase (SOD) which may be due to enhanced production of oxygen free radical and related tissue damage. The results suggest that iron-induced damage in plants can be ascribed to a direct metal action on thiols and by toxic oxygen species. An increase in lipid peroxidation product and K+ leakage are the primary responses of iron toxicity on membrane damage. However, the decrease in chlorophyll content is part of the overall expression of iron toxicity.
Antioxidants↗
Ulnar dimelia. Is it a true duplication of the ulna?
Ulnar dimelia (mirror hand) is a rare congenital disorder, characterized by duplication of the ulna, absence of the radius and polydactyly. Approximately 60 cases have been reported worldwide. We present a new case, with its own distinguishing features. These features illustrate that the aetiology of ulnar dimelia is probably failure of differentiation of a part of the ray rather than its pure duplication.
Adolescent↗
Anti-steroidogenic activity of the petroleum ether extract and fraction 5 (fatty acids) of carrot (Daucus carota L.) seeds in mouse ovary.
The petroleum ether extract and fraction 5 (fatty acids) of carrot seeds arrested the normal estrus cycle of adult mouse and reduced the weight of ovaries significantly. The cholesterol and ascorbic acid content in ovaries were significantly elevated due to the treatment with extract and fraction 5 (fatty acids) of carrot seeds. The significant inhibition of delta 5,3-beta-hydroxy steroid dehydrogenase and glucose-6-phosphate dehydrogenase, the two key enzymes involved in ovarian steroidogenesis, were also observed in mouse ovaries after 15 days of treatment. Results of this study revealed that the fraction 5 (fatty acids) present in carrot seeds acts as an antisteroidogenic agent.
Alkanes↗
Pressure modulates monocyte migration.
Migration of monocytes into the subendothelial space of the aorta has been considered to be an important event in the development of atherosclerosis. Because hypertension is commonly associated with atherosclerosis, we studied the effect of applied pressure on the migration of monocytes. Direct applied pressure increased the migration (P < .001) of monocytes across a filter when compared with normal atmospheric pressure. The migration of monocytes was found to be directly related to the amount of the applied pressure. Amlodipine, a calcium channel blocker, attenuated the migration of monocytes under normal as well as increased pressure conditions in a dose-dependent manner. These studies provide a basis to speculate on the role of direct pressure in the migration of monocytes into the subendothelial space and the possibility that vasoactive agents may modulate the migration of monocytes independent of their pressure-lowering effect.
Amlodipine↗
Inhibition of calcium oxalate urolithiasis in a rat model of lithogenesis using bisphosphonates.
Bisphosphonates bind renal calculi and inhibit calcium oxalate crystal growth in vitro. We evaluated their ability to inhibit calcium oxalate urolithiasis in a lithogenic rat model. Male Sprague-Dawley rats (four groups, eight rats each) were fed 1.0% ethylene glycol in their drinking water for 6 weeks. All rats had implantation of a 50- to 60-mg zinc pellet in their urinary bladder at the beginning of the 6-week period. The control group received no treatment. The other three groups received six weekly intraperitoneal injections of one of three bisphosphonates: pamidronate (APD), clodronate (CLO), or methylene diphosphonate (MDP). At the end of 6 weeks, the zinc pellet was retrieved and weighed; the kidneys were sectioned and stained to evaluate inflammation, tubular dilation, and crystal deposition; and blood and urine samples were analyzed for calcium and creatinine. There were no detectable biochemical differences between the control and the treatment groups. Zinc pellets removed from control animals had a significantly greater increase in weight secondary to crystal deposition than those from the treatment groups (mean 28.4% for control v 18.9%, 15.3%, and 18.6%, respectively, for animals given APD, CLO, and MDP). The control animals also had significantly higher scores for inflammation, tubular dilation, and crystal deposition than animals treated with MDP and CLO. Older and newer-generation bisphosphonates have an inhibitory effect on calcium oxalate urolithiasis that is demonstrable at relatively infrequent dosing intervals in vivo. More frequent dosing or higher doses may allow greater inhibition of stone formation.
Analgesics, Non-Narcotic↗