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PubMedDate not supplied

The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. III. Hypomorphic and hypermorphic mutations affecting the expression of hairless.

A lethal locus (l(2)br7;35B6-10), near Adh on chromosome arm 2L of D. melanogaster, is identified with Plunkett's dominant suppressor of Hairless (H). Of eight new alleles, seven act as dominant suppressors of H, the eighth is a dominant enhancer of H. One of the suppressor alleles is both a leaky lethal and a weak suppressor of H. Confirming Nash (1970), deletions of l(2)br7 are dominant suppressors, and duplications are dominant enhancers of H. A simple model is proposed to account for the interaction of l(2)br7 and H, assuming that amorphic (or hypomorphic) alleles of l(2)br7 suppress H and that hypermorphic alleles enhance H.

Alcohol Oxidoreductases↗

PubMed1977

A genetic and biochemical analysis of the temperature sensitive, normal-winged alleles of the rudimentary locus of Drosophila melanogaster.

The genetic and biochemical characteristics of a particular class of mutants at the rudimentary locus are described. The mutants are pyrimidine auxotrophs, like classical rudimentary alleles, but they are unique in that they do not alter the size or shape of the wing (Falk and Nash 1974b). Aspartate transcarbamylase and dihydroorotase activities have been measured in seven different normal-winged mutants, and the results indicate that these strains are enzymologically "leaky" mutants. Previous studies have shown that three genetic functions (corresponding to the first three enzymes of pyrimidine synthesis) are associated with the rudimentary locus. Four of the seven mutants appear to affect all three of these functions. Each of the four is temperature sensitive, and a biochemical analysis of the temperature sensitivity of one of these mutants, (r)pyr1-3, suggests that a process affecting the synthesis or assembly of these enzymes is altered at high temperatures.

Alleles↗

PubMed1980

Role of interaction energy in the specificity of transcription. I-The Watson Crick G-C base pair template.

The purpose of this work is to show that the selectivity of the nucleotide bases in RNA transcription c an be inferred, in principle, from the DNA base pair - RNA base interaction. The catalytic role of enzymes in this process is, therefore, only to form the sugar - phosphate backbone. A systematic study for the evaluation of the interaction energy of the DNA base pair with the enterant RNA bases have been undertaken to elucidate the aforesaid mechanism. Electrostatic hard sphere approximation of Nash and Bradley 1 has been employed. Non bonded induced dipole and London dispersion forces are not taken into account. The present communication gives the results of computations of the interaction energy of the four RNA bases. The results have been discussed with reference to Stent's and Zubay's schemes of RNA transcription.

Base Composition↗

PubMed1980

Role of interaction energy in the specificity of transcription. II-The Watson Crick A-U base pair template.

In continuation with work regarding the evaluation of the energy of association of various RNA bases with various base pairs, the results of the computations of the electrostatic interaction energy of A-U base pair with four RNA bases viz. Adenine, Uracil, Guanine and Cytosine have been reported. Non bonded induced polarization and dispersion potentials are not taken into account. Electrostatic hard sphere model of Nash and Bradley has been employed. Computations have been performed to find out the minimum energy configuration out of the various possible complex configurations. Results have been discussed with reference to similar calculations with G-C base pair performed by the authors.

Adenine↗

PubMed1976

Fluorometric method for assay of kallikrein-like arginine esterases.

The fluorometric method of Nash for determination of methanol was applied in assay of kallikrein-like arginine esterases using N-a-tosyl-L-arginine methyl ester (TAME) as substrate. The results obtained using this method corresponded well with those obtained in the usual colorimetric methods using hydroxamate, chromotropic acid, and 3-methyl-2-benzothiazolone hydrazone and the present method was more sensitive than these colorimetric methods.

Arginine↗

PubMed2002

Mechanisms of hepatotoxicity.

This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.

Animals↗

PubMedDate not supplied

Impact of orthoses on the rate of scoliosis progression in children with cerebral palsy.

This study was undertaken to determine the impact of spinal bracing on curve pattern and the rate of progression of neuromuscular scoliosis in children with cerebral palsy. Twenty-one patients were treated with a Wilmington custom-molded orthosis with 23 h a day brace wear for a mean bracing period of 67 months (range, 22-173). Twenty-two patients had a similar follow-up to spinal fusion but had no bracewear. Patients who were braced had a scoliosis that reached a magnitude of 50 degrees at a mean 12.5 years, compared with a mean age of 14 years for those who were not braced (p > 0.05). Spinal orthotics had no impact on scoliosis curve, shape, or rate of progression in spastic quadriplegic patients who were followed-up on fusion. Apical vertebral rotation > 2 (Nash and Moe criteria) is an indicator of impending rapid progression of the scoliosis curve.

Adolescent↗

PubMedDate not supplied

Effect of the Harrington compression system on the correction of the rib hump in spinal instrumentation for idiopathic scoliosis.

To analyze the effect of the Harrington compression system on the rib hump in thoracic idiopathic scoliosis, intraoperative measurements were made on 21 cases during correction with the distraction system and after addition of the compression system. The data show that the compression system makes a major contribution to the correction of total rib deformity in over two-thirds of the patients, and the correction of the rib valley is much more significant than correction of the rib hump. Analysis of postoperative spine roentgenograms seems to indicate that the extent of the rib correction does not correlate with spine derotation as measured by the system of Nash and Moe. The improvement in rib correction achieved by addition of the compression system appears to result from changes centered about the costovertebral joints.

Adolescent↗

PubMed2005

Non-alcoholic fatty liver disease and insulin resistance: importance of risk factors and histological spectrum.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been associated with several metabolic conditions (MC) and secondary causes, but the relationship between insulin resistance (IR) and the underlying aetiology of NAFLD has not been extensively explored. OBJECTIVE: To determine the frequency of IR among NAFLD patients and to describe IR according to risk factors and histological findings of the disease. METHODOLOGY: A case-series study of 64 patients with clinical and histological diagnosis of NAFLD. IR was calculated by homeostasis model assessment (HOMA) and IR was considered when HOMA > or = 3. Histological grades of NAFLD were: stage 1, steatosis isolated; stage 2, steatosis and inflammation; stage 3, steatosis and ballooning degeneration; stage 4, steatosis and fibrosis and/or Mallory bodies. Fibrosis was graded 0-4 (cirrhosis). RESULTS: IR was found in 21 (33%) patients. Among those with IR, 16 patients (76%) had associated MC and five patients (24%) had exposure to petrochemicals. The mean value of HOMA varied from 3.5 in NAFLD associated with MC to 1.6 in patients with exposure to petrochemicals (P < 0.03). Waist circumference was the metabolic factor most strongly associated with IR (P < 0.005). Steatohepatitis (NASH) was observed in 54 (84.3%) cases. The HOMA mean value was significantly higher in patients with advanced fibrosis. CONCLUSIONS: IR occurred in 33% of the NAFLD patients, being more frequent among those with MC than among those with exposure to petrochemicals. The presence of IR in cases with advanced fibrosis suggests that it may influence the prognosis of NAFLD.

Adult↗

PubMed2006

Tendon graft substitutes-rotator cuff patches.

Over the past few years, many biologic patches have been developed to augment repairs of large or complex tendon tears. These patches include both allograft and xenografts. Regardless of their origins, these products are primarily composed of purified type I collagen. Many factors should be considered when choosing an augmentation patch including tissue origin, graft processing, cross-linking, clinical experience, and physical properties. The purpose of this article is to familiarize the sports medicine community with several tendon augmentation grafts: GraftJacket (Wright Medical Technology, Arlington, TN), CuffPatch (Organogenesis, Canton, MA, licensed to Arthrotek, Warsaw, IN), Restore (Depuy, Warsaw, IN), Zimmer Collagen Repair (Permacol) patch (Tissue Science Laboratories Covington, GA, licensed to Zimmer, Warsaw, IN), TissueMend (TEI Biosciences, Boston, MA, licensed to Stryker Howmedica Osteonics, Kalamazoo, MI), OrthoADAPT (Pegasus Biologics, Irvine, CA), and BioBlanket (Kensey Nash, Exton, PA).

Arthroscopy↗

PubMed2003

Prediction of Cobb angle in idiopathic adolescent scoliosis.

We did a prospective study of 291 children and adolescents with idiopathic scoliosis to identify possible correlations between clinical (scoliometer value, age, height) and radiographic (Cobb angle, Nash-Moe rotation, Risser iliac apophysis classification) parameters to predict the curve angle. There was a statistically significant correlation between thoracic, thoracolumbar, and lumbar scoliometer values and the thoracic, thoracolumbar, and lumbar Cobb angles, respectively (Pearson's r-0.685, 0.572, and 0.677, respectively). There was a statistically significant correlation between Cobb angle in the thoracic, thoracolumbar, and lumbar spine and the patients' age and height. Mathematical formulas that predict the Cobb angle of thoracic, thoracolumbar, and lumbar scoliosis using the scoliometer measurements are reported.

Adolescent↗

PubMed2006

Comparison of manual and digital measurements in adolescent idiopathic scoliosis.

STUDY DESIGN: Comparison of manual and digital measurement of radiographic parameters in patients with adolescent idiopathic scoliosis (AIS). OBJECTIVE: To assess the reliability of digital measures as compared to manual measures in the evaluation of AIS. SUMMARY OF BACKGROUND DATA: Radiographic parameters are critical to the evaluation of patients with AIS, and are frequently used to monitor curve progression and guide treatment decisions. The reliability of many of the more common radiographic measures has only recently been elucidated for both manual and digital measures. However, a comparative analysis of manual versus digital measures has been performed only for coronal Cobb angles. The inter-technique reliability of these parameters will have increasing importance as digital radiographic viewing and analysis become commonplace. METHODS: There were 2 independent, blinded observers that measured 30 complete sets of preoperative (posterior-anterior, lateral, and both side-bending) and postoperative (posterior-anterior and lateral) radiographs on 4 different occasions. For the first 2 iterations, manual measurements were taken using the same pencil and protractor. For the last 2 iterations, measurements of digitized radiographs were taken on a software measurement program (PhDx, Albuquerque, NM). Coronal measures included the main thoracic and thoracolumbar/lumbar standing and side-bending Cobb angles, apical vertebral translation, coronal balance, T1 tilt angle, lowest instrumented vertebrae angle, angulation of the disc inferior to the lowest instrumented vertebrae, apical Nash-Moe vertebral rotation, and Risser grade. Sagittal parameters included T2-T5 and T5-T12 regional thoracic kyphosis, T2-T12 thoracic kyphosis, T10-L2 thoracolumbar junction sagittal curvature, T12-S1 lumbar lordosis, and global sagittal balance. The technique-dependent measurement variability and the inter-technique (manual vs. digital), intraobserver reliability were evaluated for each radiographic parameter (within 3 degrees ). RESULTS: Digital measurement showed decreased intraobserver variability for many (9 of 15) of the radiographic parameters assessed. Likewise, digital measures indicated good or excellent correlation with the absolute values obtained with manual measurement for many (10 of 15) parameters. All but 1 of those parameters having moderate-to-poor correlation had been previously shown to have poor reliability, regardless of measurement technique. Statistically significant differences between measurement variability were noted for 6 measures, including 2 favoring digital and 4, manual. Significant differences in the absolute values were noted for 5 measures, determined at a difference of 3 degrees . However, the differences in both parameter variability and absolute values tended to be small and of little clinical significance for manual versus digital measurement. CONCLUSIONS: Digital measurement showed improved measurement precision and good correlation with manual measurements for the majority of AIS parameters. Absolute differences between manual and digital measurements were generally small. Therefore, digital measures are acceptable as a valid technique for scoliosis evaluation. The importance of digital versus manual measurement reliability will increase as digital radiographic viewing becomes more prevalent.

Adolescent↗

PubMed2005

Reliability analysis for digital adolescent idiopathic scoliosis measurements.

OBJECTIVE: Analysis of adolescent idiopathic scoliosis (AIS) requires a thorough clinical and radiographic evaluation to completely assess the three-dimensional deformity. Recently, these radiographic parameters have been analyzed for reliability and reproducibility following manual measurements; however, most of these parameters have not been analyzed with regard to digital measurements. The purpose of this study is to determine the intra- and interobserver reliability of common scoliosis radiographic parameters using a digital software measurement program. METHODS: Thirty sets of preoperative (posteroanterior [PA], lateral, and side-bending [SB]) and postoperative (PA and lateral) radiographs were analyzed by three independent observers on two separate occasions using a software measurement program (PhDx, Albuquerque, NM). Coronal measures included main thoracic (MT) and thoracolumbar-lumbar (TL/L) Cobb, SB MT Cobb, MT and TL/L apical vertical translation (AVT), C7 to center sacral vertical line (CSVL), T1 tilt, LIV tilt, disk below lowest instrumented vertebra (LIV), coronal balance, and Risser, whereas sagittal measures included T2-T5, T5-T12, T2-T12, T10-L2, T12-S1, and sagittal balance. Analysis of variance for repeated measures or Cohen three-way kappa correlation coefficient analysis was performed as appropriate to calculate the intra- and interobserver reliability for each parameter. RESULTS: The majority of the radiographic parameters assessed demonstrated good or excellent intra- and interobserver reliability. The relationship of the LIV to the CSVL (intraobserver kappaa = 0.48-0.78, fair to excellent; interobserver kappaa = 0.34-0.41, fair to poor), interobserver measurement of AVT (rho = 0.49-0.73, low to good), Risser grade (intraobserver rho = 0.41-0.97, low to excellent; interobserver rho = 0.60-0.70, fair to good), intraobserver measurement of the angulation of the disk inferior to the LIV (rho = 0.53-0.88, fair to good), apical Nash-Moe vertebral rotation (intraobserver rho = 0.50-0.85, fair to good; interobserver rho = 0.53-0.59, fair), and especially regional thoracic kyphosis from T2 to T5 (intraobserver rho = 0.22-0.65, poor to fair; interobserver rho = 0.33-0.47, low) demonstrated lesser reliability. In general, preoperative measures demonstrated greater reliability than postoperative measures, and coronal angular measures were more reliable than sagittal measures. CONCLUSIONS: Most common radiographic parameters for AIS assessment demonstrated good or excellent reliability for digital measurement and can be recommended for routine clinical and academic use. Preoperative assessments and coronal measures may be more reliable than postoperative and sagittal measurements. The reliability of digital measurements will be increasingly important as digital radiographic viewing becomes commonplace.

Adolescent↗

PubMed2005

Behavior of various orbital implants under axial compression.

PURPOSE: To determine and compare the amount of force required to disrupt the integrity of various orbital implants. METHODS: Compression tests were carried out by using a servo-electrical universal testing system on orbital implants including aluminum oxide (Bioceramic implant, FCI, Issy-Les-Moulineaux, France), coralline hydroxyapatite (HA) (Bio-Eye, Integrated Orbital Implants, Inc., San Diego, CA, U.S.A.), bovine HA (Molteno M-Sphere, IOP Inc., Costa Mesa, CA, U.S.A.), synthetic HA (FCI3, FCI, Issy-Les-Moulineaux, France), Chinese HA (H + Y Comprehensive technologies, Philadelphia, PA, U.S.A.), polylactic acid (Kinsey Nash Corporation, Duluth, MN, U.S.A.), porous polyethylene (Medpor, Porex Surgical Inc., College Park, GA, U.S.A.), and polymethylmethacrylate. RESULTS: Two basic groups of implants were identified: those that eventually reach a critical compression point and collapse (coralline HA, aluminum oxide, synthetic FCI3 HA, bovine HA, Chinese HA, and polymethylmethacrylate), and those that do not collapse but gradually compress with increasing load (porous polyethylene, polylactic acid). For similar-sized implants, the critical collapse point was earliest for the FCI3 HA implant, followed by the coralline HA, aluminum oxide, and polymethylmethacrylate implants. Smaller-sized collapsible implants showed earlier critical collapse points than larger-sized implants of similar material. CONCLUSIONS: A technique was established to assess the force required to disrupt the integrity of various orbital implants that is reliable, unbiased, and repeatable with any orbital implant. Orbital implants of different materials and sizes demonstrate different degrees of integrity. It is important to use similar-sized implants when comparing the integrity of different implant materials because size influences the force required to overcome the structural integrity of the implant.

Aluminum Oxide↗

PubMed2001

Natural selection of the critical period for language acquisition.

The language acquisition period in humans lasts about 13 years. After puberty it becomes increasingly difficult to learn a language. We explain this phenomenon by using an evolutionary framework. We present a dynamical system describing competition between language acquisition devices, which differ in the length of the learning period. There are two selective forces that play a role in determining the critical learning period: (i) having a longer learning period increases the accuracy of language acquisition; (ii) learning is associated with certain costs that affect fitness. As a result, there exists a limited learning period which is evolutionarily stable. This result is obtained analytically by means of a Nash equilibrium analysis of language acquisition devices. Interestingly, the evolutionarily stable learning period does not maximize the average fitness of the population.

Biological Evolution↗

PubMed2004

Chaos and language.

Human language is a complex communication system with unlimited expressibility. Children spontaneously develop a native language by exposure to linguistic data from their speech community. Over historical time, languages change dramatically and unpredictably by accumulation of small changes and by interaction with other languages. We have previously developed a mathematical model for the acquisition and evolution of language in heterogeneous populations of speakers. This model is based on game dynamical equations with learning. Here, we show that simple examples of such equations can display complex limit cycles and chaos. Hence, language dynamical equations mimic complicated and unpredictable changes of languages over time. In terms of evolutionary game theory, we note that imperfect learning can induce chaotic switching among strict Nash equilibria.

Biological Evolution↗

PubMed2007

Negotiation of mutualism: rhizobia and legumes.

The evolution and persistence of biological cooperation have been an important puzzle in evolutionary theory. Here, we suggest a new approach based on bargaining theory to tackle the question. We present a mechanistic model for negotiation of benefits between a nitrogen-fixing nodule and a legume plant. To that end, we first derive growth rates for the nodule and plant from metabolic models of each as a function of material fluxes between them. We use these growth rates as pay-off functions in the negotiation process, which is analogous to collective bargaining between a firm and a workers' union. Our model predicts that negotiations lead to the Nash bargaining solution, maximizing the product of players' pay-offs. This work introduces elements of cooperative game theory into the field of mutualistic interactions. In the discussion of the paper, we argue for the benefits of such an approach in studying the question of biological cooperation.

Biological Evolution↗

PubMed2001

Q learning in the minority game.

We present a numerical investigation of the minority game model, where the dynamics of the agents is described by the Q-learning algorithm. The numerical results show that the Q-learning dynamics is suppressing the "crowd effect," which is characteristic of the minority game with standard inductive dynamics, and it converges to a stationary state that is close to the optimal Nash equilibrium of the game.

Journal Article↗