Central role of arachidonate 5-lipoxygenase in the regulation of cell growth and apoptosis in human prostate cancer cells.
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Apoptosis↗
Biomedical subjects
J Ghosh
Publications and source records attributed to J Ghosh.
Comparison of treatment outcomes with banded and bonded RPE appliances.
The purpose of this retrospective study was to compare the treatment outcomes with a banded (n = 38) versus a bonded (n = 55) rapid palatal expansion appliance followed by edgewise orthodontics. Both lateral cephalometric radiographs and orthodontic study casts were evaluated at pretreatment and posttreatment time periods. Overall, the banded rapid palatal expansion group had more vertical change than the bonded group. However, most of these changes were less than 1 degrees or 1 mm and may be considered clinically insignificant. This study could not establish superiority of one type of rapid palatal expansion technique over another.
Adolescent↗
Lipoxygenase inhibition in prostate cancer.
Multiple population-based studies show an increased risk of prostate cancer in populations that consume large amounts of animal fat. However, the molecular mechanisms linking dietary fat to prostate cancer biology remain obscure. Animal fats are typically rich sources of arachidonic acid and this fatty acid is converted to a wide range of powerful compounds including leukotrienes, prostaglandins, etc. We have shown that PC3 and LNCaP convert arachidonic acid to the 5-lipoxygenase product, 5-HETE. When the formation of 5-HETE is blocked, human prostate cancer cells enter apoptosis in less than 1 h and are dead within 2 h. Exogenous 5-HETE can rescue these cancer cells. These findings indicate that 5-HETE is a potent survival factor for human prostate cancer cells.
Aged↗
Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells.
Diets high in fat are associated with an increased risk of prostate cancer, although the molecular mechanism is still unknown. We have previously reported that arachidonic acid, an omega-6 fatty acid common in the Western diet, stimulates proliferation of prostate cancer cells through production of the 5-lipoxygenase metabolite, 5-HETE (5-hydroxyeicosatetraenoic acid). We now show that 5-HETE is also a potent survival factor for human prostate cancer cells. These cells constitutively produce 5-HETE in serum-free medium with no added stimulus. Exogenous arachidonate markedly increases the production of 5-HETE. Inhibition of 5-lipoxygenase by MK886 completely blocks 5-HETE production and induces massive apoptosis in both hormone-responsive (LNCaP) and -nonresponsive (PC3) human prostate cancer cells. This cell death is very rapid: cells treated with MK886 showed mitochondrial permeability transition between 30 and 60 min, externalization of phosphatidylserine within 2 hr, and degradation of DNA to nucleosomal subunits beginning within 2-4 hr posttreatment. Cell death was effectively blocked by the thiol antioxidant, N-acetyl-L-cysteine, but not by androgen, a powerful survival factor for prostate cancer cells. Apoptosis was specific for 5-lipoxygenase-programmed cell death was not observed with inhibitors of 12-lipoxygenase, cyclooxygenase, or cytochrome P450 pathways of arachidonic acid metabolism. Exogenous 5-HETE protects these cells from apoptosis induced by 5-lipoxygenase inhibitors, confirming a critical role of 5-lipoxygenase activity in the survival of these cells. These findings provide a possible molecular mechanism by which dietary fat may influence the progression of prostate cancer.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
High fidelity of internal strand transfer catalyzed by human immunodeficiency virus reverse transcriptase.
A system to study the fidelity of internal strand transfer events was constructed. A donor RNA, on which reverse transcriptase (RT)-directed DNA synthesis was initiated, shared homology with an acceptor RNA, to which DNAs initiated on the donor could transfer. The homology occurred over a 119-base internal region of the donor which coded for the N-terminal portion of the alpha-lac gene. Polymerase chain reaction (PCR) was used to amplify DNA synthesis products. The PCR products were then digested with PvuII and EcoRI and ligated into a vector which had this same region excised. Transformed Escherichia coli were screened for the ability to produce a functional beta-galactosidase protein by blue-white phenotype analysis with white colonies scored as those with errors in alpha-lac. Products synthesized on the donor were used to assess the error rate of human immunodeficiency virus-RT while products transferring to and subsequently extended on the acceptor (transfer products) were used to monitor transfer fidelity. Human immunodeficiency virus-RT made approximately 1 error per 7500 bases copied in the assay. Nucleocapsid protein (NCp), although stimulating strand transfer 3-fold, had no effect on RT fidelity. Transfer products in the absence of NCp had essentially the same amount of errors as donor-directed products while those produced with NCp showed a slight increase in error frequency. Overall, strand transfer events on this template were highly accurate. Since experiments with other templates have suggested that transfer is error prone, the fidelity of strand transfer may be highly sequence dependent.
Base Sequence↗
Perioral forces and dental changes resulting from mandibular lip bumper treatment.
This prospective study compares pretreatment and posttreatment forces produced by a lip bumper on the mandibular first molars and determines the dental effects of this appliance after 1 year of treatment. Twenty-five patients, ages 10 to 17 years, received fixed 0.045-inch passive stainless steel lip bumpers positioned at the level of the gingival margin, 2 mm from the labial surface of the teeth as the only form of treatment in the mandibular arch. At the end of 1 year, cephalometric radiographs and dental casts were taken, and lower lip forces remeasured during rest, speech, and swallowing. Lip force measurements were performed using specially designed strain gauges mounted bilaterally in the lip bumper tubes. Measurements of lip forces made before and after treatment were compared to explore the changes, if any, due to muscle adaptation to the appliance. Dental changes were measured from casts and cephalometric radiographs. Correlation analyses were performed to determine whether a relationship existed between initial force levels and resulting tooth movement. Pretreatment and posttreatment forces did not demonstrate a statistically significant difference. On the other hand, measurement of the dental casts revealed a significant increase in arch length caused by incisor proclination and protrusion, combined with molar distalization. The arch width significantly increased at the canines, first and second premolars, and first molars. The amount of force exerted by the lower lip on the molars was not correlated to the degree of tooth movement recorded in this sample.
Adaptation, Physiological↗
Arachidonic acid metabolism and cancer of the prostate.
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Arachidonic Acid↗
Ensembles of radial basis function networks for spectroscopic detection of cervical precancer.
The mortality related to cervical cancer can be substantially reduced through early detection and treatment. However, current detection techniques, such as Pap smear and colposcopy, fail to achieve a concurrently high sensitivity and specificity. In vivo fluorescence spectroscopy is a technique which quickly, noninvasively and quantitatively probes the biochemical and morphological changes that occur in precancerous tissue. A multivariate statistical algorithm was used to extract clinically useful information from tissue spectra acquired from 361 cervical sites from 95 patients at 337-, 380-, and 460-nm excitation wavelengths. The multivariate statistical analysis was also employed to reduce the number of fluorescence excitation-emission wavelength pairs required to discriminate healthy tissue samples from precancerous tissue samples. The use of connectionist methods such as multilayered perceptrons, radial basis function (RBF) networks, and ensembles of such networks was investigated. RBF ensemble algorithms based on fluorescence spectra potentially provide automated and near real-time implementation of precancer detection in the hands of nonexperts. The results are more reliable, direct, and accurate than those achieved by either human experts or multivariate statistical algorithms.
Algorithms↗
Iatrogenic Cushing's syndrome.
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Anti-Inflammatory Agents↗
Arachidonic acid stimulates prostate cancer cell growth: critical role of 5-lipoxygenase.
Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a member of the omega-6 poly-unsaturated fatty acids, was found to be an effective stimulator of human prostate cancer cell growth in vitro at micromolar concentrations. Selective blockade of the different metabolic pathways of arachidonic acid (e.g. ibuprofen for cyclooxygenase, SKF-525A for cytochrome P-450, baicalein and BHPP for 12-lipoxygenase, AA861 and MK886 for 5-lipoxygenase, etc.) revealed that the growth stimulatory effect of arachidonic acid is inhibited by the 5-lipoxygenase specific inhibitors, AA861 and MK886, but not by others. Addition of the eicosatetraenoid products of 5-lipoxygenase (5-HETEs) showed stimulation of prostate cancer cell growth similar to that of arachidonic acid, whereas the leukotrienes were ineffective. Moreover, the 5-series of eicosatetraenoids could reverse the growth inhibitory effect of MK886. Finally, prostate cancer cells fed with arachidonic acid showed a dramatic increase in the production of 5-HETEs which is effectively blocked by MK886. These experimental observations suggest that arachidonic acid needs to be metabolized through the 5-lipoxygenase pathway to produce 5-HETE series of eicosatetraenoids for its growth stimulatory effects on human prostate cancer cells.
Arachidonate 5-Lipoxygenase↗
On Hebbian-like adaptation in heart muscle: a proposal for 'cardiac memory'.
Studies on the effects of external pacing of heart suggest that the organ, like the nervous system, possesses the properties of 'memory' and adaptation. Changes induced in cardiac activation patterns persist long after the agent that induced those changes itself is removed. After the effects of stimulation have disappeared, response to the stimulus applied for a second time is much greater than the earlier response. Motivated by such results, this paper further explores the possibility of a 'cardiac memory'. In particular, we point out that communication via gap junctions in cardiac tissue is similar to synaptic conductance in nervous tissue and demonstrate, with the aid of a mathematical model, that cardiac tissue can exhibit memory-like behavior if gap-junctional conductances are allowed to adapt according to a Hebbian-like mechanism.
Adaptation, Physiological↗
Forces produced by lip bumpers on mandibular molars.
The purpose of this study was to measure the forces produced by a lip bumper on the mandibular permanent first molars. The forces in a sample of 38 patients were measured bilaterally with specially designed gauges at rest but with their lips lightly touching, speaking the words church, phone, and pop, and swallowing water. Forces were compared between two types of lip bumpers, i.e., wire or shield, and between various anteroposterior and vertical positions of the lip bumper. The resting forces produced by the wire lip bumper 2 mm anterior to the incisors and vertically positioned at the middle of the incisor crown were 5.93 +/- 4.84 gm for the left side and 4.66 +/- 4.8 gm for the right. The forces were found to be significantly higher when the wire lip bumper was placed 4 mm anterior to the incisors and at a more gingival position, measuring 16.68 +/- 8.7 gm for the left side and 13.88 +/- 8.28 gm for the right. The shield lip bumper had higher forces both at the center of the incisor as well as when it was positioned gingivally. A large individual variation was observed. There were no statistically significant differences in force levels between male and female subjects. Speaking the words church, pop, and phone, produced forces between 11 and 23 gm, using a wire lip bumper. Swallowing produced the highest forces, between 32 and 36 gm. Lip thickness and height did not appear to affect the force levels.
Acrylic Resins↗
Stiffness-deflection behavior of selected orthodontic wires.
Treatment of horizontal and vertical tooth discrepancies requires wires of low stiffness to produce forces as the teeth are leveled and aligned. In this investigation, the stiffness characteristics of several solid and multistrand nickel-titanium and stainless steel orthodontic wires were determined at selected clinically relevant deflections. Twenty specimens of 24 different wires were tested in both three-point and three-bracket bending modes. The unloading force deflection plot of each wire was described by a polynomial regression from which wire stiffnesses were obtained by mathematical differentiation. Graphs of the functional relationship between stiffness and deflection are presented. The results of this investigation show that wire stiffness can be altered not only by changing the size, but also by varying the number of strands and the alloy composition. An equally important finding was the dependence of stiffness on deflection for most of the wires measured. Comparisons were also made between the stiffness values obtained in three-point bending and the three-bracket bending systems.
Dental Alloys↗
Evaluation of stresses and forces in selected I-bars using the finite element method.
PURPOSE: Three-dimensional models of half-round, tapered and full-round, untapered I-bar clasps of varying configurations and material properties were constructed. The purpose of this study was to examine the stresses and reaction forces produced within each model upon deflection to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm) at 1 mm from the tip using the finite element method. MATERIALS AND METHODS: Three-dimensional computer models of half-round and full-round clasps were constructed using solid eight-node brick elements. The half-round, tapered I-bar clasp model was 2.4 and 1.4 mm in diameter at the base and tip, respectively. The full-round, untapered I-bar clasp model was 1 mm in diameter. Three design groups were created for each clasp form. Group A had 25% of the total length in the straight anchor end of the I-bar clasp, B had 35%, and C had 50%. All models were 31 mm in length and had a radius of curvature of 5 mm. Different material properties were incorporated into the models. Each model was deflected at a point 1 mm from the tip to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm). RESULTS: The stresses and forces produced as a result of the deflection applied to each clasp were viewed and displayed graphically. The maximum von Mises stresses in megapascals and the reaction force in newtons (N) were recorded. Stresses varied in each clasp in the range of 0 to 154.3 MPa for the half-round, tapered I-bar clasp models, and 0 to 100.9 MPa for the full-round I-bar clasp models at 0.01-in deflection. Reaction force measured near the tip of the clasp models was between 1.60 N and 6.31 N for the half-round, and between 0.22 N to 2.13 N for the full-round I-bar clasp models. For all clasps studied, as the deflection increased, the location of stress within each group remained the same regardless of the material properties; however, the stress and force values increased linearly. CONCLUSIONS: The location of maximum stress varied with the length of the anchor portion of the clasps studied. Maximum stresses were located on the flat side of the half-round, tapered I-bar clasp model.
Color↗
The effects of exogenous prostaglandin E2 on root resorption in rats.
This study evaluated the amount and depth of root resorption associated with varying concentrations and frequencies of injectable, exogenous prostaglandin E2 (PGE2) in conjunction with orthodontic tooth movement in rats. The sample consisted of 155 maxillary right and left first molars from 88, 8-week old, male Sprague-Dawley rats. The animals were divided into three control groups and two experimental groups. The control animals were divided into one nonappliance and two appliance groups. The experimental animals were divided into 2- and 4-week experimental time periods that were further subdivided based on single and weekly injection intervals of PGE2 and four different injectable concentration levels, i.e., 0.1, 1.0, 5.0, and 10.0 micrograms. A fixed orthodontic appliance was ligated between the maxillary incisors and maxillary first molars with closed-coil nickel-titanium springs. The appliance had an initial activating force of 60 gm. Serial histologic sections of the mesial root of the maxillary first molar were made, and a quantitative histomorphometric analysis of root resorption on the mesial and distal surfaces was performed. This study demonstrated increased root surface resorption when using exogenous PGE2 injections to enhance orthodontic tooth movement over a 2-week period with increasing root resorption on the mesial surface as compared with the distal surface in PGE2 treated teeth. No differences in root resorption were found with either multiple injections or increasing concentration in the 4-week experimental group. Local injection of PGE2 appeared to have no effect on the number or depth of resorption lacunae in either the 2- or 4-week groups.
Analysis of Variance↗
A longitudinal cephalometric study of the soft tissue profile of short- and long-face syndromes from 7 to 17 years.
The longitudinal growth and development of the soft tissue drape for boys and girls with long and short vertical patterns was examined from age 7 to 17 years. The sample was taken from the Denver Growth Study and consisted of 32 subjects who were selected on the basis of their percentage of lower anterior vertical face height. All subjects were of northern European ancestry, and none had undergone orthodontic treatment. The sexual dimorphism was evident as anticipated for several soft tissue measurements. The boys showed continued growth through age 16 years in contrast to the girls who attained the adult size of the soft tissue integument around 14 years. A significant difference between vertical facial patterns was reported for all soft tissue variables with the exception of the soft tissue thickness at A point and the upper lip height. The boys and girls with long vertical patterns exhibited a thicker and longer soft tissue drape for the most variables when compared with those with short facial patterns. These soft tissue differences are believed to be compensatory mechanisms in long-face subjects, which may attempt to mask the vertical dysplasia, thereby producing a more normal facial profile. Individual growth assessments revealed that the perioral soft tissues follow a pattern similar to that of the mean group patterns. The subjects with long vertical facial patterns experienced their pubertal growth spurt earlier than the short-face subjects. This may have clinical implications in the timing of orthodontic intervention and treatment.
Adolescent↗
Evaluation of an intraoral maxillary molar distalization technique.
The purpose of this study was to determine the effects of the pendulum appliance on distalization of maxillary molars and the reciprocal effects on the anchor premolars and maxillary incisors. Initial and follow-up cephalometric radiographs were obtained on 41 subjects (26 girls and 15 boys) who were treated with the pendulum appliance for bilateral distalization of the maxillary first molar teeth, for correction of the Class II molar relationship or for gaining space in the maxillary arch. Dental casts were available on 31 patients. Dental, skeletal, and soft tissue changes were determined. The mean maxillary first molar distalization was 3.37 mm, with a distal tipping of 8.36 degrees. The mean reciprocal mesial movement of the first premolar was 2.55 mm, with a mesial tipping of 1.29 degrees. The maxillary first molar position intruded 0.1 mm, whereas the first premolar extruded 1.7 mm. The transverse width between the mesiobuccal cusps of the first molars increased 1.40 mm. The maxillary second molars were also distalized 2.27 mm, tipped distally 11.99 degrees, and moved buccally 2.33 mm. The effect of distalization on the maxillary third molars was extremely variable. The eruption of maxillary second molars had minimal effect on distalization of first molars. The lower anterior face height increased by 2.79 mm. This increase was greater in patients with higher Frankfort-mandibular plane angle measurements. The pendulum appliance is an effective and reliable method for distalizing maxillary molars, provided the anchor unit is adequately reinforced. Its major advantages are minimal dependence on patient compliance, ease of fabrication, one-time activation, adjustment of the springs if necessary to correct minor transverse and vertical molar positions, and patient-acceptance.
Adolescent↗
Class II, Division 1 malocclusion treated with molar distalization therapy.
A case report of an 11-year-old black girl with a Class II, Division 1 malocclusion is presented. There was associated lip incompetence and excessive display of gingiva on smiling. Nonextraction treatment was undertaken with distalization of maxillary molars to correct the Class II relationship. [This case was presented at the annual session of the American Association of Orthodontists held in Orlando, 1994. This was part of the University of Oklahoma, Department of Orthodontics participation in the display of patients treated by graduate students sponsored by the College of Diplomates, American Board of Orthodontics.]
Cephalometry↗