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Spine growth precedes synapse formation in the adult neocortex in vivo.

Dendritic spines appear and disappear in an experience-dependent manner. Although some new spines have been shown to contain synapses, little is known about the relationship between spine addition and synapse formation, the relative time course of these events, or whether they are coupled to de novo growth of axonal boutons. We imaged dendrites in barrel cortex of adult mice over 1 month, tracking gains and losses of spines. Using serial section electron microscopy, we analyzed the ultrastructure of spines and associated boutons. Spines reconstructed shortly after they appeared often lacked synapses, whereas spines that persisted for 4 d or more always had synapses. New spines had a large surface-to-volume ratio and preferentially contacted boutons with other synapses. In some instances, two new spines contacted the same axon. Our data show that spine growth precedes synapse formation and that new synapses form preferentially onto existing boutons.

Age Factors↗

Anti-oestrogenic prevention of breast cancer--the make or break point.

Clinical trials have shown that giving anti-oestrogens to healthy women can reduce the early incidence of breast cancer by approximately 40%. However, the large numbers of women treated, compared with the few who get breast cancer, together with the not insignificant toxicity and the unknown long-term clinical benefits and risks, makes this strategy of prevention versus treatment precarious. So how can we improve the odds for the successful use of endocrine chemoprevention?

Antineoplastic Agents, Hormonal↗

The mammalian Golgi--complex debates.

Since the first description of the Golgi in 1898, key issues regarding this organelle have remained contentious among cell biologists. Resolving these complex debates, which revolve around Golgi structure-function relationships, is prerequisite to understanding how the Golgi fulfils its role as the central organelle and sorting station of the mammalian secretory pathway.

Animals↗

The contribution of imaging and digitised data to mandibular reconstruction and implant stabilised occlusal rehabilitation: a case report.

Different methods are recommended for the surgical reconstruction of the resected mandible. The advantages for implant stabilised prostheses in restoring the occlusion are recognised but few papers provide adequate data to identify the successful outcome of treatment. The literature is reviewed and the advantages of imaging together with the use of digitised data is highlighted by a case requiring rehabilitation with enhanced planning methods.

Bone Transplantation↗

Magnetic resonance imaging: a useful tool for evaluation of bone prior to implant surgery.

OBJECTIVE: To illustrate the potential for use of magnetic resonance imaging (MRI) to gain full sectional information before placement of osseo-integrated dental implants, with no patient exposure to ionising radiation. MATERIALS AND METHODS: Four typical cases are illustrated, the patients being imaged in a one tesla MRI scanner. The setting up of the sequences is explained, along with the use of an imaging/surgical template with gadolinium markers. RESULTS: MRI clearly shows full sectional detail of available bone for safe implant placement, and allows the delineation of cortical and cancellous bone to attain maximum implant length and stability. Vital structures and the floor of the maxillary sinus are clearly shown. CONCLUSIONS: MRI allows the surgeon to assess cases for suitability to place dental implants with confidence. The ability to scan directly at any desired plane, with no reformatting, and to relate this information to a surgical template gives predictable surgery. MRI is a sectional imaging modality giving information about the 3-dimensional relationship of the vital structures, without using ionising radiation. It therefore deserves consideration as an alternative to computed tomography. However, further work is indicated to investigate the relative technical merits of the two imaging modalities.

Adult↗

A developmental biological study of aldolase gene expression in Xenopus laevis.

We cloned cDNAs for Xenopus aldolases A, B and C. These three aldolase genes are localized on different chromosomes as a single copy gene. In the adult, the aldolase A gene is expressed extensively in muscle tissues, whereas the aldolase B gene is expressed strongly in kidney, liver, stomach and intestine, while the aldolase C gene is expressed in brain, heart and ovary. In oocytes aldolase A and C mRNAs, but not aldolase B mRNA, are extensively transcribed. Thus, aldolase A and C mRNAs, but not B mRNA, occur abundantly in eggs as maternal mRNAs, and strong expression of aldolase B mRNA is seen only after the late neurula stage. We conclude that aldolase A and C mRNAs are major aldolase mRNAs in early stages of Xenopus embryogenesis which proceeds utilizing yolk as the only energy source. aldolase B mRNA, on the other hand, is expressed only later in development in tissues which are required for dietary fructose metabolism. We also isolated the Xenopus aldolase C genomic gene (ca. 12 kb) and found that its promoter (ca. 2 kb) contains regions necessary for tissue-specific expression and also a GC rich region which is essential for basal transcriptional activity.

Amino Acid Sequence↗

Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane.

Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. However, little is known about the specialized trafficking events occurring at the postsynaptic membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in receptor targeting. Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a complex physically associated, but not yet fused with the postsynaptic membrane. Electron microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.

Animals↗

Predicting penile size during erection.

The aim of this prospective study was to identify clinical and engineering parameters of the flaccid penis for prediction of penile size during erection. Dorsal and ventral penile lengths, as well as base and tip circumferences were measured in flaccid states, gently stretched states and at full erection resulting from intracavernosal injection of prostaglandin E1 in 55 patients. The forces required to stretch the penis were measured by a specially designed gauge and regression relationships of the measured dimensions were calculated. An engineering model was developed to analyze differences between results obtained during stretching and erection, as well as to approximate the optimal force values which should be applied during the stretching part of the clinical evaluation of penile size. The ratio between the flaccid to stretched penile lengths was shown to be the best predictor for the ventral elongation from flaccid to erect penile lengths. The engineering analysis predicted that a minimal tension force of approximately 450 g during stretching of the penis is required to reach the potential erection length. The stretching forces exerted by the urologist in the clinical setting were experimentally shown to be significantly (P<0.01) less than this value. The values of the relative and absolute elongations of the stretched penis at its ventral aspect provide reliable estimations of its potential maximal elongation during erection. The model designed for this study may obviate the use of intracavernosal injections for estimating penile length during erection.

Adult↗

Biomechanical aspects of Peyronie's disease in development stages and following reconstructive surgeries.

Peyronie's disease is a disorder of the penile connective tissues that leads to development of dense fibrous or ossified plaques in the tunica albuginea, causing penile deformity and painful erection. A biomechanical model of the penis was utilized for analyzing the mechanical stresses that develop within its soft tissues during erection in the presence of Peyronie's plaques. The model's simulations demonstrated stress concentrations around nerve roots and blood vessels due to the plaques. These stresses may irritate nerve endings or compress the vascular bed, and thus cause penile deformity and/or painful erection. The model was further used to elaborate the effects of different biological or artificial materials for reconstruction of the penis following plaque removal. Clinical applications of the present model can range from analysis of the etiology of the disease to assisting in the determination of optimal timing for therapeutic interventions and in the selection of patch material for penile reconstructions.

Biomechanical Phenomena↗

Lateral biopsies added to the traditional sextant prostate biopsy pattern increases the detection rate of prostate cancer.

Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error and data based upon whole-mounted step-sectioned radical prostatectomy specimens using a three-dimensional computer-assisted prostate biopsy simulator suggests that an increased detection rate is possible using laterally placed biopsies. The simulated 10-core biopsy pattern (traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland) was shown to be superior to the traditional sextant biopsy. The objective of this pilot study was to confirm the higher prostate cancer detection rate obtained using the 10-core biopsy pattern in patients. We reviewed data on 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core biopsy pattern. The frequency of positive biopsy was determined for each core. Additionally, the sextant and 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3%(19/35) were diagnosed by the sextant biopsy only. The 10-core pattern resulted in an additional 45.7%(16/35) of patients being diagnosed solely with the laterally placed biopsies. The laterally placed biopsies had the highest frequency of positive biopsies when compared to the sextant cores. In conclusion, biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Prostate Cancer and Prostatic Diseases (2000) 3, 43-46

Journal Article↗

Hemodynamic stresses and structural remodeling of anastomosing arteriolar networks: design principles of collateral arterioles.

OBJECTIVE: To investigate the potential influence of hemodynamic stresses on the development of the arcade arteriole (AA) network during normal maturation. METHODS: AA network data were collected from ink-filled Wistar-Kyoto rat gracilis muscles and used to construct hemodynamic computational models of the AA network at 7 (WKY(7)) and 13 (WKY(13)) weeks of age. RESULTS: Mean coefficients of variation for pressure, circumferential wall stress, and wall shear stress were 0.13, 0.12, and 0.48, respectively. Wall shear rate variability across bifurcations generated deviations in mean energy cost that were 9-30% above theoretical minimum, with many bifurcations exhibiting substantially higher energy costs. With the exception of the lowest pressure AA segments, the monotonic relationship between wall shear stress and pressure in the AAs was nearly identical from 7 to 13 weeks of age. CONCLUSIONS: Low coefficients of variation for computed AA pressures indicate that an even pressure head is maintained over the muscle during remodeling of the AA network. The anastomotic structure of the network creates high shear rate variability that, in turn, creates high-energy costs in some regions of the network. The results are consistent with the hypothesis that, during development, the maintenance of mean circumferential wall stress and the pressure-shear stress relationship are operative design principles for collateral arteriole development.

Animals↗

The heart is already working.

Understanding the logic of living systems requires knowledge of the mechanisms involved at the levels at which functionality is expressed. This information resides neither in the genome, nor even in the individual proteins that genes code for. No functionality is expressed at these levels. It emerges as the result of interactions between many proteins relating to each other in multiple cascades and in interaction with the cellular environment. There is therefore no alternative to copying nature and computing these interactions to determine the logic of healthy and diseased states. The rapid growth in biological databases, models of cells, tissues and organs and the development of powerful computing hardware and algorithms have made it possible to explore functionality in a quantitative manner all the way from the level of genes to the physiological function of whole organs and regulatory systems. I use models of the heart to demonstrate that we can now go all the way from individual genetic information (on mutations, for example) to exploring the consequences at a whole-organ level.

Coronary Circulation↗

Stiffness of incisor segments of edgewise arches in torsion and bending.

A mechanical model dentition is used in a laboratory study to relate incisor segment third-order activation to actual torque induced upon engagement of maxillary Edgewise arches. A portion of the sample of stainless-steel aches was subjected to stress-relief heat treatment. Torsional stiffness values are calculated, and the accompanying vertical displacement force on the incisor segment is evaluated. The results seem to warrant the following conclusions. Broad ranges of incisor segment torque magnitudes may be obtained from rectangular orthodontic wires and arch designs presently in common clinical use. Torsional behavior is associated with the elastic shear modulus or modulus of rigidity, which is essentially the same for all stainless and chrome-cobalt alloys. Vertical extrusive force is generated as a secondary effect directly related to the torsional stiffness and torque activation. Compensation is possible through archwire adjustments to cause the wire to lie above the bracket slots of the incisor segment before activation of lingual root torque. Stress relief of rectangular stainless steel arches following placement of V-bends, twists, or loops did not have a significant effect on force values. Further investigation, modeling other configurations such as labiolingual movements of the six maxillary anterior teeth to determine the torsional stiffnesses for commonly-used arches could be worthwhile. Similarly, the quantification of torsional stiffnesses of arches fabricated in rectangular nickel-titanium, titanium-molybdenum, and braided stainless-steel wires may be of value.

Biomechanical Phenomena↗

The effect of long-term deflection on permanent deformation of nickel-titanium archwires.

The clinician must now consider the alloy along with cross-sectional shape and size when selecting archwires. The purpose of this study is to quantify permanent deformation after long-term deflection of available nickel-titanium archwires. Nine nickel-titanium, one beta-titanium and one stainless steel archwires, .016 inch round, were deflected into orthodontic brackets of simulated archform. One lateral incisor was positioned to yield a deflection of 5 mm in a lingual direction. After wire deactivation, deformation was measured at 1, 14, and 28 days. Two-way ANOVA and Tukey's critical difference tests were used to determine statistical differences. The nickel-titanium wires exhibited better springback characteristics and less permanent deformation than the stainless steel and TMA wires. Several wires increased deformation as deflection time increased. No clinically significant difference was found between presently available nickel-titanium wires in terms of permanent deformation, long- or short-term.

Analysis of Variance↗

Rotary Ni-Ti profile systems for preparing curved canals in resin blocks: influence of operator on instrument breakage.

AIM: The aim of this study was to determine the incidence of fracture of ProFile 0.4 and 0.6 taper Series 29 nickel-titanium instruments with respect to operator experience. METHODOLOGY: A total of 125 simulated root canals in resin blocks with the same geometrical shape in terms of angle and radius of curvature and coronal and apical orifice diameter were used. Five operators prepared all the specimens using an identical step-down instrument sequence, each one preparing 25 canals. The operators included two endodontists and three general practitioners. Statistical data concerning the incidence of instrument failure was compiled using Statlab and Fisher's partial least square difference analysis of variance. RESULTS: A total of 21 (16.8%) instruments fractured, all had 0.04 tapers. Nine size 25 instruments failed, 9 size 20 instruments failed and 3 size 15. During the study, the Binary Tree analysis of instrument failure revealed two operator populations belonging to two different study periods. The first period, which represented the first 13 root canal preparations, was called the 'learning period', and the second period, which represented the next 12 sample preparations, was called the 'application period'. A greater number of instruments failed during the first period than during the second. In the 'learning period', both groups of operators learned the same way. In the 'application period', two groups could be distinguished; the first group consisted of a general practitioner who produced worse results, and the second group consisted of the other four operators. CONCLUSIONS: The results indicate the necessity of mastering this rotary canal preparation technique, and the importance of improving competence through learning and experience.

Clinical Competence↗

The use of computed tomography when comparing nickel-titanium and stainless steel files during preparation of simulated curved canals.

AIM: The aim of this study was to compare canal preparations completed with Hedstrom and K-files of ISO size 15 - 40, made of nickel-titanium (Ni-Ti) and stainless steel (SS). METHODOLOGY: Eighty simulated canals with 200 and 30 degrees C curvatures were prepared using the step-back technique and quarter turn/pull instrument manipulation. Middle and apical level canal sections were taken using computed tomography. RESULTS: No significant difference was found between any of the file types at either level with respect to canal curvature (20 degrees or 30 degrees). At the middle level, the stainless steel files caused more enlargement toward the inner part, compared to nickel-titanium files. At the apical level, nickel-titanium canal files caused more enlargement toward the inner part, whereas more outward enlargement was caused by stainless steel instruments. No significant difference could be observed at the middle level (P > 0.05) related to the enlargement toward the outer side of the canal curvature. Transportation at both levels was significantly less (P < 0.001) for the Ni-Ti files than the SS ones. Centring ratios of the file types at the middle level were low, but not significantly different (P > 0.05), whereas at the apical level the centring ratios were significantly higher for the Ni-Ti files (P < 0.001). CONCLUSIONS: Ni-Ti instruments produced preparations with adequate enlargement, less transportation, and a better centring ratio.

Dental Instruments↗

A comparative study of lateral condensation, heat-softened gutta-percha, and a modified master cone heat-softened backfilling technique.

AIM: The aim of the study was to compare the quality of root fillings completed by lateral condensation (L), Thermafil (TF), and a new technique using Thermafil for backfilling (BF), with special emphasis on control of overfilling. METHODOLOGY: Sixty curved canals in plastic blocks were prepared with the ProFile system to size 40/04 taper in the apical half and to 06 taper in the coronal half. The canals were divided into three groups of 20. Apical patency was verified with a size 15 K-file. The canals were then filled using three different techniques: LC (20 canals), TF (20 canals), and BF, where a size 40 master point with sealer was seated prior to the introduction of a size 30 Thermafil point (20 canals). The same resin-based sealer was used on each occasion. The root fillings were assessed using stereo-microscopy for material extrusion, digital radiography for occurrence of voids, and microscopy of sections for voids and thickness of sealer layer. RESULTS: Extrusion of both gutta-percha and sealer occurred in all 20 canals filled with the TF technique, but only three and five cases of sealer extrusion were detected with LC and BF techniques, respectively. No voids were detected in the TF group, whereas small voids were present in most fillings in the LC and BF groups. The average total length of the voids was less than 1 mm per canal. The thickness of the sealer layer in the middle and apical parts was greater in the LC and BF groups than in the TF group. CONCLUSIONS: LC and BF techniques resulted in fewer overfills than TF. Voids were absent in TF fillings, whilst small voids were found in the LC and BF groups.

Dental Pulp Cavity↗