Computer model of a bovine type I collagen microfibril

It has been found that > 60% of bipolar I and almost 50% of bipolar II patients have a history of substance abuse (Regier et al., 1990). While previous studies have examined comorbidity of bipolar disorder and substance abuse, little has been done to examine the effect of substance abuse on the course of bipolar disorder. There has also been little distinction made between bipolar disorder occurring prior to substance abuse and that occurring after the onset of substance abuse. Given the high prevalence of substance abuse in bipolar patients, it would be useful to determine more about the effect of substance abuse on demographic and clinical features and on the course of illness. We attempted to do this with a retrospective chart review of 188 bipolar patients seen by D.L. Dunner between January 1992 and December 1993. Demographic and clinical information as well as information about course of illness were systematically extracted from the charts. We compared the means and percentages of these variables and analysed them for significance. Preliminary results show differences in demographics, clinical features and course of illness between patient groups. These differences may illustrate the clinical effects of substance abuse on the course of bipolar disorder. Our results also indicate that there are differences between patients whose bipolar disorder began prior to and those whose disorder began after the onset of substance abuse.     

A consensus model for molecular packing of type I collagen

In this review, recent results from X-ray diffraction studies of tendon are used to develop an understanding of the molecular packing of type I collagen in tendon fibrils. These cover the definition of the unit cell as triclinic, the lateral architecture of molecular packing in a fibril and the molecular packing topology of a structure that gives good agreement with X-ray diffraction data. The proposed model is a 1D staggered left handed microfibril; the molecular orientation of the telopeptides indicates that there are interconnections between microfibrils that may explain the difficulty in isolating individual microfibrillar structures. This is the first structure that defines the absolute molecular packing of molecular segments based on X-ray diffraction data. These results are discussed in the light of direct and indirect evidence relating to molecular packing such as mineralization, natural crosslink position, and biomechanical evidence. The ability of the proposed structure to fulfill many of the structural and biochemical criteria point towards the structure providing a basis for a consensus model of collagen packing.     

Molecular bending and networks in a basement membrane-like collagen: packing in dogfish egg capsule collagen

Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. Data available on the effects of technical-grade PCP on the immune system are insufficient and equivocal; some data indicate inhibitory effects, whereas others suggest stimulating effects. This study was performed to evaluate toxicological and immune findings in 32 subjects who had prolonged exposure to PCP in a wood factory and in 37 controls. PCP concentrations were determined in plasma and urine of all subjects. Lymphocyte subsets of CD3-, CD4-, and CD8-positive cells were evaluated, and the proliferative response of peripheral blood mononuclear cells (PBM) to mitogens was assessed. The results suggested the absence of major laboratory and clinical signs of PCP-dependent immune deficiency. A weak effect of long-term exposure to PCP on the functional immune response could not be ruled out because of the finding of a decreased response to 5% PHA in the high-exposure group. A weak effect against hepatocyte membrane was evidenced by the finding of raised serum concentration of glycocholic, taurodeoxycholic, and glycochenodeoxycholic acids in subjects directly exposed to PCP for more than 10 y.     

Computational and experimental study of turbulent flow in a 0.4-scale water model of a continuous steel caster

Single-phase turbulent flow in a 0.4-scale water model of a continuous steel caster is investigated using large eddy simulations (LES) and particle image velocimetry (PIV). The computational domain includes the entire submerged entry nozzle (SEN) starting from the tundish exit and the complete mold region. The results show a large, elongated recirculation zone in the SEN below the slide gate. The simulation also shows that the flow exiting the nozzle ports has a complex time-evolving pattern with strong cross-stream velocities, which is also seen in the experiments. With a few exceptions, which are probably due to uncertainties in the measurements, the computed flow field agrees with the measurements. The instantaneous jet is seen to have two typical patterns: a wobbling “stair-step” downward jet and a jet that bends upward midway between the SEN and the narrow face. A 51-second time average suppressed the asymmetries between the two halves of the upper mold region. However, the instantaneous velocity fields can be very different in the two halves. Long-term flow asymmetry is observed in the lower region. Interactions between the two halves cause large velocity fluctuations near the top surface. The effects of simplifying the computational domain and approximating the inlet conditions are presented.     

Cell behavior and signal molecule involvement in a case study of malignant histiocytosis: a negative model of morphine as an immunoregulator

OBJECTIVE: This paper identifies specific data items for use by state and local agencies in a maternal and child oral health needs assessment model. METHODS: A modified Delphi approach was used to develop consensus on items for inclusion in the data set and their relative importance. Initially, 31 data items were chosen from several national sources. All state dental directors, along with other selected administrators and advisory committee members for this process, were asked to categorize each of the data items as core (essential), important but optional, or of lesser importance. Short comments about each data item were accepted, as were additions to the list of data items. Two rounds of comments were held. RESULTS: Eleven data items/types of information were selected as core items to be included in all needs assessments. All but one of these items were determined by the scores of the respondents. The advisory committee strongly recommended that at least one core item relate to the public's perception of oral health. Some differences in perceived importance of several items existed among the state dental directors, local dental directors, and the advisory committee. Twenty-one items were identified as being important, but optional, and seven were considered less than important and not included in the model data set. CONCLUSIONS: A modified Delphi approach facilitated the development of core and optional data items for a model oral health needs assessment. This model has potential for a common reporting mechanism so that states and local dental programs can share data.     

Nerve length and volume in synaptic vs diffusion neurotransmission: a model

Non-synaptic diffusion neurotransmission (NDN) may be an important factor in brain space and energy conservation, especially within cell assemblies and for mass sustained functions. We have illustrated the extreme cases of total synaptic and total ND neurotransmission for the purpose of noting the differences between the two. For these modeling studies, in which we assume assemblies of 1000 to 100 000 cells supplied by at least one fiber and a single synapse from each of the other cells, each cell assembly would have approximately 200 m to 8000 km of nerve fibers more than when innervated by diffusion. For coeruleo-cortical synaptic innervation, linking each to a common origin (the locus coeruelus), the fiber lengths are 38 cm (1000 cells) to 170 m (100,000 cells). It is likely , however, that neuronal arrays include both 'wireless' (NDN) as well as synaptic intercellular communication systems.     

Esophageal anastomosis: an experimental model to study anastomotic healing and the use of lyophilized collagen

This experimental study assessed the use of lyophilized collagen to reinforce cervical esophageal anastomosis in rabbits. Twenty New Zealand White rabbits weighing 2.3-3.2 kg were used. In group I (n = 10) a 1-cm-long segment of the esophagus was excised and the two free edges anastomosed, to mimic the conditions found in newborn esophageal atresia. Group II (n = 10) had a segmental esophageal resection and end-to-end anastomosis as in group I but the anastomotic site was circumferentially covered with lyophilized type I collagen film. The resected segments were processed immediately and served as controls for the postoperative tissue in each animal. The animals were starved for the first 24 h and water was given on the 2nd postoperative day; on the 3rd postoperative day the animals were allowed a normal diet. Two rabbits in group II died on the 7th and 8th postoperative days because of a fistula. All the rabbits were killed on the 10th postoperative day and 4-cm segments of esophagus with the anastomosis at the centre were removed. At this time gross leakage was detected in four animals (one in group I and three in group II). Each anastomosis was evaluated for bursting pressure, collagen content, and histologic appearance. Bursting pressure was higher in group I. Collagen (measured as hydroxyproline) levels in anastomotic and adjoining 1-cm segments were compared with concentrations in control segments resected during operation. In group II animals there was a significant reduction in the lowering of hydroxyproline concentrations around the anastomosis. Microscopic evaluation revealed no significant differences between the two groups. This experiment showed no demonstrable benefit from the use of lyophilized collagen in preventing the esophageal anastomotic leakage that occurs in repaired esophageal atresia.     

Reasons adolescents don't use drugs: exploring a "depth of acceptance" model

Adolescent's reasons for not using drugs were examined for evidence of factors that might lead to differential resistance to drug use. Six thousand eight-hundred and forty-one sixth, eighth, tenth, and twelfth grade students were administered a comprehensive drug survey which included: 1) demographic information, 2) reasons not to use drugs, and 3) self-reports of lifetime and current (30-day) drug use across sixteen drug categories. The reasons for not using drugs were then factor analyzed and the results compared to a "Depth of Acceptance" (DOA) model consisting of four orientations: External Outcome, Social, and Personal. These orientations are thought both to represent distinct immunization factors and to be differentially related in strength to lifetime and current drug use. Confirmatory factor analysis revealed a close fit between the hypothesized orientations and factor loadings among the sixteen items. Collectively, the sixteen items were also found to be excellent predictors of both lifetime and current drug use. While multiple stepwise regression analyses did reveal differential predictive strengths between orientation and drug use, the misclassification of a single item apparently attenuated the results for Social Orientation. The DOA model appears to provide a useful framework for "fine-tuning" prevention messages based on factors that immunize against drug use.     

A comparative cerebral blood flow study in a baboon model with acetazolamide provocation: 99mTc-HMPAO vs 123I(IMP)

Pharmacological interactions are important when nuclear medical procedures are applied to patients under drug therapy, or drug provocation. This study compares in baboon models (regional) cerebral blood flow [(r)CBF] results from 99mTc-HMPAO and 123I-iodoamphetamine [123I(IMP)] each with and without acetazolamide, the latter a suggested drug for testing cerebrovascular reserve. Expected differences in cerebral uptake were observed between the two radio-tracers without acetazolamide. The increase in tracer uptake resulting from acetazolamide is significantly enhanced for 123I(IMP), which could have diagnostic implications.     

Posatirelin in the treatment of vascular dementia: a double-blind multicentre study vs placebo

INTRODUCTION: The usefulness of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide), a synthetic peptide having modulatory activity on the monoaminergic and cholinergic systems and neurotrophic effects, was evaluated in vascular dementia. PATIENTS AND METHODS: A multicentre, parallel groups, double-blind clinical study vs placebo was carried out with patients suffering from probable vascular dementia according to the NINDS-AIREN criteria. The study consisted of a two-week run-in of a once daily, orally administered, placebo phase, followed by 12 weeks of intramuscular treatment with posatirelin 10 mg/ml or placebo given once a day and a follow-up after one month's withdrawal. Efficacy was assessed using the Gottfries-Br?ne-Steen (GBS) Rating Scale for dementia, the Randt Memory Test and the Toulouse-Piéron Attention Test. Data were evaluated using analysis of variance and covariance. RESULTS: As regards GBS scores, patients treated with posatirelin showed a significant improvement in intellectual performance, in orientation, motivation and memory as compared to controls. The improvement of memory performance was also confirmed by the acquisition score and memory index of the Randt Memory Test. At the end of the follow-up period the differences between treatments were still maintained. Tolerability was good. CONCLUSIONS: The significant improvement observed in cognitive functions, attention and motivation of demented patients treated with posatirelin suggests the potential usefulness of this drug in vascular dementia. Furthermore, the presence of a long-lasting effect after drug withdrawal suggests the possibility of administering the drug cyclically.     

Computational analysis of flow in a curved tube model of the coronary arteries: effects of time-varying curvature

The flow through a curved tube whose radius of curvature varies with time was studied in order to better understand flow patterns in coronary arteries. A computational flow model was constructed using commercially available software. The artery model featured a uniform circular cross section, and the curvature was assumed to be constant along the tube, and in one plane. The computational model was verified with the use of a dynamically similar in vitro apparatus. A steady uniform velocity was prescribed at the entrance at a Reynolds number of 300. Two sets of results were obtained: one in which the curvature was held constant at the mean, maximum and minimum radii of curvature (quasistatic), and another in which the curvature was varied sinusoidally in time at a frequency of I Hz (dynamic). The results of the dynamic analysis showed that the wall shear rates varied as much as 52% of the static mean wall shear rate within a region of 10 tube diameters from the inlet. The results of the dynamic analysis were within 6% of the quasistatic predictions. Realistic modeling of the deforming geometry is important in determining which locations in the coronary arteries are subjected to low and oscillating wall shear stresses, flow patterns that have been associated with atherogenesis.     

Computational model of obsessive-compulsive disorder: examination of etiologic hypothesis and treatment strategies

Research has shown that obsessive compulsive disorder (OCD) is related to structural and functional abnormalities in the brain, and several authors have organized these findings into theories of OCD neuropsychiatric dysfunction. In this paper, these theories were used to develop a neural network model of OCD. OCD symptoms were hypothesized to result from a hyperactive orbitofrontal-striato-thalamic-orbitofrontal neural loop. The network was constructed and trained with a backpropagation algorithm, and it was then used to assess etiologic theories of OCD (e.g., basal ganglia dysfunction, inadequate dopaminergic inhibitory influence on basal ganglia and excessive input from the limbic system). The network was also observed in analogues of the treatment of OCD with serotonergic medications and behavior therapy. Results show that a) the network behaved both normally and abnormally, depending on what combinations of perceptual, motivational, and neurochemical inputs were presented to it; b) several etiologic mechanisms produced changes in the networks' behaviors similar to patients' subjective experiences of OCD symptoms; and c) different treatment strategies, both those modeled as pharmacologic and behavioral therapies, produced reductions in simulated OCD symptoms.     

"Prototypes in the mist: The early epochs of category learning": Correction to Smith and Minda (1998).

Reports an error in "Prototypes in the mist: The early epochs of category learning" by J. David Smith and John Paul Minda (Journal of Experimental Psychology: Learning, Memory, and Cognition, 1998[Nov], Vol 24[6], 1411-1436). As a result of errors made in production, two equations in the article were printed incorrectly. The corrected equations are included in the erratum. (The following abstract of the original article appeared in record 1998-12790-005.) Recent ideas about category learning have favored exemplar processes over prototype processes. However, research has focused on small, poorly differentiated categories and on task-final performances--both may highlight exemplar strategies. Thus, we evaluated participants' categorization strategies and standard categorization models at successive stages in the learning of smaller, less differentiated categories and larger, more differentiated categories. In the former case, the exemplar model dominated even early in learning. In the latter case, the prototype model had a strong early advantage that gave way slowly. Alternative models, and even the behavior of individual parameters within models, suggest a psychological transition from prototype-based to exemplar-based processing during category learning and show that different category structures produce different trajectories of learning through the larger space of strategies. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Grafting of enzymes on collagen films using Woodward''s reagent "K" and a water-soluble carbodiimide derivative

Two new methods of activation were developed to graft enzymes on collegen films. They involved chemical modifications of surface groups of collagen either by Woodward's reagent "K" or by EDC, a water-soluble derivative of carbodiimide. EDC was a better coupling agent and a detailed study was conducted with this agent. It could be used either in a global method of activation and coupling, or in a two-step procedure of activation of collagen, followed by spontaneous coupling of enzyme. All enzymes tested were successfully bound: malate dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, urease, creatine kinase, hexokinase. The influence on the yield of grafted enzyme, of pretreatment of films, time and temperature of EDC activation, concentration of EDC and enzyme, protecting agents was studied. Stability of enzyme activity on storage was greatly increased after grafting. A co-grafted dual system creatine kinase/heoxkinase, was achieved which exhibited a good efficiency. A striking renaturing process at 0-4degreesC after thermal denaturation, was observed with hexokinase.