Designing a new two-dimensional molecular layout by hydrogen bonding.
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Journal Article↗
Biomedical subjects
M Abel
Publications and source records attributed to M Abel.
Synchronization of organ pipes: experimental observations and modeling.
We report measurements on the synchronization properties of organ pipes. First, we investigate influence of an external acoustical signal from a loudspeaker on the sound of an organ pipe. Second, the mutual influence of two pipes with different pitch is analyzed. In analogy to the externally driven, or mutually coupled self-sustained oscillators, one observes a frequency locking, which can be explained by synchronization theory. Further, we measure the dependence of the frequency of the signals emitted by two mutually detuned pipes with varying distance between the pipes. The spectrum shows a broad "hump" structure, not found for coupled oscillators. This indicates a complex coupling of the two organ pipes leading to nonlinear beat phenomena.
Journal Article↗
CNS somatosensory-auditory interactions elicit or modulate tinnitus.
Evidence has accumulated linking clinical tinnitus to the somatosensory system. Most clinical tinnitus patients can change the psychoacoustic attributes of their tinnitus with forceful head and neck contractions. The significance of such somatic modulation of tinnitus was assessed by testing non-clinical subjects. Like clinical tinnitus patients, about 80% of non-clinical subjects who had ongoing tinnitus at the time of testing (whether or not they had been previously aware of it) could modulate their tinnitus with head and neck contractions. Almost 60% of those with no tinnitus at the time of testing could elicit a tinnitus-like auditory percept with head and neck contractions. Because similar results were found in the profoundly deaf, we conclude that somatosensory-auditory interactions within the central nervous system account for most, if not all, somatic modulation of tinnitus as well as the development of auditory percepts with somatic testing. Other observations implicate the muscle spindle as initiating the neural activation that ultimately modulates the central auditory pathway, including the dorsal cochlear nucleus. Somatic influences upon auditory perception are not limited to tinnitus subjects but are a fundamental property of the auditory system.
Adolescent↗
Differentiation of adult-type Leydig cells occurs in gonadotrophin-deficient mice.
During mammalian testis development distinct generations of fetal and adult Leydig cells arise. Luteinising hormone (LH) is required for normal adult Leydig cell function and for the establishment of normal adult Leydig cell number but its role in the process of adult Leydig cell differentiation has remained uncertain. In this study we have examined adult Leydig cell differentiation in gonadotrophin-releasing hormone (GnRH)-null mice which are deficient in circulating gonadotrophins. Adult Leydig cell differentiation was assessed by measuring expression of mRNA species encoding four specific markers of adult Leydig cell differentiation in the mouse. Each of these markers (3beta-hydroxysteroid dehydrogenase type VI (3betaHSD VI), 17beta-hydroxysteroid dehydrogenase type III (17betaHSD III), prostaglandin D (PGD)-synthetase and oestrogen sulphotransferase (EST)) is expressed only in the adult Leydig cell lineage in the normal adult animal. Real-time PCR studies showed that all four markers are expressed in adult GnRH-null mice. Localisation of 3betaHSD VI and PGD-synthetase expression by in situ hybridisation confirmed that these genes are expressed in the interstitial tissue of the GnRH-null mouse. Treatment of animals with human chorionic gonadotrophin increased expression of 3betaHSD VI and 17betaHSD III within 12 hours further indicating that differentiated, but unstimulated cells already exist in the GnRH-null mouse. Thus, while previous studies have shown that LH is required for adult Leydig cell proliferation and activity, results from the present study show that adult Leydig cell differentiation will take place in animals deficient in LH.
17-Hydroxysteroid Dehydrogenases↗
[Campaign to eradicate yaws on Santo Island, Vanuatu in 2001].
At the beginning of the 1960s a campaign was carried out to eradicate endemic trepanematosis in the South Pacific. During the year 2000, twenty cases of yaws were diagnosed on Santo Island in Vanuatu. Recrudescence of this disease was confirmed by a seroprevalence testing showing 20.9% positive VDRL in 273 serum tests. In view of these findings, the Health Minister in collaboration with the WHO office in Vanuatu undertook mass benzathine-benzylpenicilline treatment in the population of the Santo and Malo (SANMA) province. The objective was to treat at least 85% of the population. Treatment was administered to 36,414 of the 39,397 inhabitants identified in 587 villages during the campaign, i.e., 92.4%. Coverage varied from 87.6 to 97.3% depending on the zone. Positive VDRL was obtained in 96 of the 230 serum samples collected for suspicion of yaws. All documented cases of yaws were found in the southeastern part of the island. Treatment had a dramatic effect on lesions within 24 hours. Cooperation of the population and involvement of mobile units and primary health-care providers were key factors in the success of this campaign. Further action will include training of health care workers and improvement of sanitary conditions in villages. Seroprevalence testing to assess the effectiveness of this campaign is to be carried out in 2003.
Adolescent↗
Pattern dynamics of vortex ripples in sand: nonlinear modeling and experimental validation.
Vortex ripples in sand are studied experimentally in a one-dimensional setup with periodic boundary conditions. The nonlinear evolution, far from the onset of instability, is analyzed in the framework of a simple model developed for homogeneous patterns. The interaction function describing the mass transport between neighboring ripples is extracted from experimental runs using a recently proposed method for data analysis, and the predictions of the model are compared to the experiment. An analytic explanation of the wavelength selection mechanism in the model is provided, and the width of the stable band of ripples is measured.
Journal Article↗
OPUS study: suicidal behaviour, suicidal ideation and hopelessness among patients with first-episode psychosis. One-year follow-up of a randomised controlled trial.
BACKGROUND: Patients with first-episode psychosis comprise a high-risk group in terms of suicide. AIMS: To identify predictive factors for suicidal behaviour and to examine the effect of integrated treatment on suicidal behaviour and hopelessness. METHOD: A total of 341 patients with a first-episode schizophrenia-spectrum disorder were randomised to integrated treatment or treatment as usual. RESULTS: During the 1-year follow-up period, 11% attempted suicide. This was associated with female gender, hopelessness, hallucinations and suicide attempt reported at baseline, with the two latter variables being the only significant ones in the final multivariate model. The integrated treatment reduced hopelessness. CONCLUSIONS: Hallucinations and suicide attempt before inclusion in the study were the most significant predictors of suicide attempt in the follow-up period.
Adolescent↗
Front propagation in laminar flows.
The problem of front propagation in flowing media is addressed for laminar velocity fields in two dimensions. Three representative cases are discussed: stationary cellular flow, stationary shear flow, and percolating flow. Production terms of Fisher-Kolmogorov-Petrovskii-Piskunov type and of Arrhenius type are considered under the assumption of no feedback of the concentration on the velocity. Numerical simulations of advection-reaction-diffusion equations have been performed by an algorithm based on discrete-time maps. The results show a generic enhancement of the speed of front propagation by the underlying flow. For small molecular diffusivity, the front speed V(f) depends on the typical flow velocity U as a power law with an exponent depending on the topological properties of the flow, and on the ratio of reactive and advective time scales. For open-streamline flows we find always V(f) approximately U, whereas for cellular flows we observe V(f) approximately U(1/4) for fast advection and V(f) approximately U(3/4) for slow advection.
Journal Article↗
Presteady-state kinetics of Bacillus 1,3-1,4-beta-glucanase: binding and hydrolysis of a 4-methylumbelliferyl trisaccharide substrate.
In the present study the first stopped-flow experiments performed on Bacillus 1,3-1,4-beta-glucanases are reported. The presteady-state kinetics of the binding of 4-methylumbelliferyl 3-O-beta-cellobiosyl-beta-D-glucoside to the inactive mutant E134A, and the wild-type-catalysed hydrolysis of the same substrate, were studied by measuring changes in the fluorescence of bound substrate or 4-methylumbelliferone produced. The presteady-state traces all showed an initial lag phase followed by a fast monoexponential phase leading to equilibration (for binding to E134A) or to steady state product formation (for the wild-type reaction). The lag phase, with a rate constant of the order of 100 s(-1), was independent of the substrate concentration; apparently an induced-fit mechanism governs the formation of enzyme-substrate complexes. The concentration dependencies of the observed rate constant of the second presteady-state phase were analysed according to a number of reaction models. For the reaction of the wild-type enzyme, it is shown that the fast product formation observed before steady state is not due to a rate-determining deglycosylation step. A model that can explain the observed results involves, in addition to the induced fit, a conformational change of the productive ES complex into a form that binds a second substrate molecule in a non-productive mode.
Amino Acid Substitution↗
Mechanism of the family 1 beta-glucosidase from Streptomyces sp: catalytic residues and kinetic studies.
The Streptomyces sp. beta-glucosidase (Bgl3) is a retaining glycosidase that belongs to family 1 glycosyl hydrolases. Steady-state kinetics with p-nitrophenyl beta-D-glycosides revealed that the highest k(cat)/K(M) values are obtained with glucoside (with strong substrate inhibition) and fucoside (with no substrate inhibition) substrates and that Bgl3 has 10-fold glucosidase over galactosidase activity. Reactivity studies by means of a Hammett analysis using a series of substituted aryl beta-glucosides gave a biphasic plot log k(cat) vs pK(a) of the phenol aglycon: a linear region with a slope of beta(lg) = -0.8 for the less reactive substrates (pK(a) > 8) and no significant dependence for activated substrates (pK(a) < 8). Thus, according to the two-step mechanism of retaining glycosidases, formation of the glycosyl-enzyme intermediate is rate limiting for the former substrates, while hydrolysis of the intermediate is for the latter. To identify key catalytic residues and on the basis of sequence similarity to other family 1 beta-glucosidases, glutamic acids 178 and 383 were changed to glutamine and alanine by site-directed mutagenesis. Mutation of Glu178 to Gln and Ala yielded enzymes with 250- and 3500-fold reduction in their catalytic efficiencies, whereas larger reduction (10(5)-10(6)-fold) were obtained for mutants at Glu383. The functional role of both residues was probed by a chemical rescue methodology based on activation of the inactive Ala mutants by azide as exogenous nucleophile. The E178A mutant yielded the beta-glucosyl azide adduct (by (1)H NMR) with a 200-fold increase on k(cat) for the 2,4-dinitrophenyl glucoside but constant k(cat)/K(M) on azide concentration. On the other hand, the E383A mutant with the same substrate gave the alpha-glucosyl azide product and a 100-fold increase in k(cat) at 1 M azide. In conclusion, Glu178 is the general acid/base catalyst and Glu383 the catalytic nucleophile. The results presented here indicate that Bgl3 beta-glucosidase displays kinetic and mechanistic properties similar to other family 1 enzymes analyzed so far. Subtle differences in behavior would lie in the fine and specific architecture of their respective active sites.
Amino Acid Substitution↗
Pulley anatomy for the radial side of the wrist.
This is the first presentation in the literature of a radial tendon flexor pulley in the distal forearm adjacent to the flexor carpi radialis. The clinical significance is that in performing wrist tendon arthroplasty, this structure and, in close proximity, the sensory branch of the median nerve may be encountered. Whether cutting the pulley of the flexor carpi radialis is clinically significant in changing wrist biomechanics is unknown.
Cadaver↗
Differential effects of 7-OH-DPAT on the development of behavioral sensitization to apomorphine and cocaine.
The primary objective of this study was to determine whether concurrent treatments with a low dose of the dopamine D(3)-preferring receptor agonist 7-OH-DPAT would attenuate the development of behavioral sensitization to the indirect dopamine receptor agonist, cocaine, or the direct dopamine receptor agonist, apomorphine. In two experiments, male Wistar rats (250-350 g) were given seven daily injections of 7-OH-DPAT (0.05 mg/kg sc) or vehicle in combination with either cocaine (15 mg/kg ip), apomorphine (1.0 mg/kg sc), or vehicle. After the injections, the rats were tested for activity in photocell arenas for 40 min, and three measures of motor behavior (distance traveled, rearing, and stereotypy) were recorded at 10-min intervals. A total of 24 h after the last preexposure session, all rats were given a challenge injection of either cocaine (10.0 mg/kg ip, Experiment 1) or apomorphine (1.0 mg/kg sc, Experiment 2) and tested for activity. Major findings were as follows: (a) 7-OH-DPAT treatments alone suppressed all measures of locomotor activity and did not affect subsequent behavioral sensitivity to either cocaine or apomorphine; (b) cocaine treatments acutely increased all measures of activity, and repeated treatments produced behavioral sensitization to the horizontal locomotor-activating effects of cocaine; (c) apomorphine treatments alone increased horizontal activity and stereotypy but completely abolished rearing behavior; (d) like cocaine, repeated treatments with apomorphine induced behavioral sensitization; (e) concurrent treatments of 7-OH-DPAT with cocaine acutely attenuated cocaine-induced increases in motor behavior but enhanced the development of behavioral sensitization to cocaine; and (f) concurrent 7-OH-DPAT treatments did not significantly affect either the acute or chronic effects of apomorphine. It is evident from these results that concurrent treatment with 7-OH-DPAT does not block the development of behavioral sensitization to either cocaine or apomorphine. Moreover, the differential acute and chronic effects of 7-OH-DPAT on cocaine- and apomorphine-induced hyperactivity appear to be mediated by dopamine autoreceptor stimulation.
Animals↗
Vasculitis following treatment of rheumatoid arthritis with extracorporeal staphylococcal protein a immunoadsorption column (prosorba).
We report a case of vasculitis after Prosorba treatment in a patient with rheumatoid arthritis. The patient is a 66-year-old white male with long standing rheumatoid arthritis and hepatitis B. He was treated with the standard regimen for Prosorba treatment. He improved and met criteria for an American College of Rheumatology (ACR) 20% response. While on therapy he developed a nonhealing ulcer. Approximately 2 weeks after treatment was completed, he developed palpable purpura and mononeuritis multiplex. Deep dermal biopsy confirmed the presence of both small and medium vessel vasculitis. Nerve conductions studies were consistent with neuropathic conduction delays. He was treated with 1mg/kg/day of oral prednisone. Prosorba has been reported to cause leukocytoclastic vasculitis during treatment, but has not been noted to involve medium sized vessels. This patient's history and presentation are most consistent with rheumatoid arthritis associated vasculitis, though the Prosorba treatment cannot be ruled out as a cause or a contributing factor. Importantly, although Prosorba treated his synovitis, it did not prevent concomitant vasculitis.
Journal Article↗
Pathophysiology of immune-mediated (type 1) diabetes mellitus: potential for immunotherapy.
Type 1 diabetes mellitus is a chronic T cell-mediated disease resulting from autoimmune destruction of pancreatic beta-cells. This process leads to progressive and irreversible failure of insulin secretion. Development of the disease involves both genetic and environmental factors. Genetic predisposition is mainly connected with the human leucocyte antigen (HLA) region, which encodes structures responsible for antigen presentation. A comprehensive molecular understanding of the pathogenesis of the disease is essential for the design of rational and well tolerated means of prevention. This paper describes recent experimental and clinical findings and elucidates the current possibilities for immunotherapy of type 1 diabetes. The nature of breakdown of self-tolerance and the mechanisms involved in its recovery are discussed.
Diabetes Mellitus, Type 1↗
Cervical spine anomalies and tumors in Weaver syndrome.
Weaver syndrome is an autosomal dominant disorder comprising accelerated growth rate and rapidly advancing skeletal maturation. Previous reports suggest that the phenotype in adults may be sufficiently subtle to make diagnosis difficult. Half brothers with classical childhood findings of Weaver syndrome and their father with minimal clinical findings showed cervical spine anomalies that likely represent a consistent radiographic finding in this disorder. One of the children represents the third occurrence of neoplasia in Weaver syndrome.
Adolescent↗
Exit-time approach to epsilon-entropy.
An efficient approach to the calculation of the epsilon-entropy is proposed. The method is based on the idea of looking at the information content of a string of data, by analyzing the signal only at the instants when the fluctuations are larger than a certain threshold epsilon, i.e., by looking at the exit-time statistics. The practical and theoretical advantages of our method with respect to the usual one are shown by the examples of a deterministic map and a self-affine stochastic process.
Journal Article↗
Electrocardiographic findings in a middle-aged African population in the Seychelles islands.
This study describes major electrocardiogram (ECG) measurements and diagnoses in a population of African individuals; most reference data have been collected in Caucasian populations and evidence exists for interethnic differences in ECG findings. This study was conducted in the Seychelles islands (Indian Ocean) and included 709 black individuals (343 men and 366 women) aged 25 to 64 years randomly selected from the general population. Resting ECG were recorded by using a validated ECG unit equipped with a measurement and interpretation software (Cardiovit AT-6, Schiller, Switzerland). The epidemiology of 14 basic ECG measurements, 6 composite criteria for left ventricular hypertrophy and 19 specific ECG diagnoses including abnormal rhythms, conduction abnormalities, repolarization abnormalities, and myocardial infarction were examined. Substantial gender and age differences were found for several ECG parameters. Moreover, tracings recorded in African individuals of the Seychelles differed from those collected similarly in Caucasian populations in many respects. For instance, heart rate was approximately 5 beats per minute lower in the African individuals than in selected Caucasian populations, prevalence of first degree atrio-ventricular block was especially high (4.8%), and the average Sokolow-Lyon voltage was markedly higher in African individuals of the Seychelles compared with black and white Americans. The integrated interpretation software detected "old myocardial infarction" in 3.8% of men and 0% of women and "old myocardial infarction possible" in 6.1% and 3%, respectively. Cardiac infarction injury scores are also provided. In conclusion, the study provides reference values for ECG findings in a specific population of people of African descent and stresses the need to systematically consider gender, age, and ethnicity when interpreting ECG tracings in individuals.
Adult↗
Surgical approaches for the management of idiopathic thoracic scoliosis and the indications for combined anterior-posterior technique.
The indications for surgical intervention in patients with idiopathic scoliosis have been well defined. The goals of surgery are to achieve fusion and arrest progressive curvature while restoring normal coronal and sagittal balance. As first introduced by Harrington, posterior fusion, the gold standard of treatment, has a proven record of success. More recently, anterior techniques for performing fusion procedures via either a thoracotomy or a retroperitoneal approach have been popularized in attempts to achieve better correction of curvature, preserve motion segments, and avoid some of the complications of posterior fusion such as the development of the flat-back syndrome. Anterior instrumentation alone, although effective, can be kyphogenic and has been shown to be associated with complications such as pseudarthrosis and instrumentation failure. Performing a combined approach in patients with scoliosis and other deformities has become an increasingly popular procedure to achieve superior correction of deformity and to minimize later complications. Indications for a combined approach (usually consisting of anterior release, arthrodesis with or without use of instrumentation, and posterior segmental fusion) include: prevention of crankshaft phenomenon in juvenile or skeletally immature adolescents; correction of large curves (75 degrees ) or excessively rigid curves in skeletally mature or immature patients; correction of curves with large sagittal-plane deformities such as thoracic kyphosis (> 90 degrees ) or thoracic lordosis (> 20 degrees ); and correction of thoracolumbar curves that need to be fused to the sacrum. Surgery may be performed either in a staged proceedure or, more commonly, in a single sitting. The authors discuss techniques for combined surgery and complication avoidance.
Journal Article↗