Role In Long-term Maintenance Research Articles

Keratinized Tissue Grafting May Prevent Peri-implantitis: A Case Series.

The necessity of a minimum volume of keratinized tissue around implants to maintain tissue stability remains a matter of debate. The aim of this case series is to showcase the outcome and long-term maintenance of dental implants that received soft tissue augmentation. Three cases of second stage following dental implant placement were evaluated for amount of keratinized tissue. Based on the Ono-Nevins classification described here, treatment was rendered including keratinized tissue grafting. The cases were followed for 10, 18 and 28 years. Each case demonstrated maintenance of soft and hard tissue profile around the dental implants with no incidence of peri-implantitis as evidenced on clinical examination and use of peri-apical radiographs. Soft tissue management around dental implants may play a key role in long-term maintenance of peri-implant health and prevention of peri-implantitis.

Cholesterol Protects Against Acute Stress-Induced T-Tubule Remodeling in Mouse Ventricular Myocytes.

Efficient excitation-contraction coupling in ventricular myocytes depends critically on the presence of the t-tubular network. It has been recently demonstrated that cholesterol, a major component of the lipid bilayer, plays an important role in long-term maintenance of the integrity of t-tubular system although mechanistic understanding of underlying processes is essentially lacking. Accordingly, in this study we investigated the contribution of membrane cholesterol to t-tubule remodeling in response to acute hyposmotic stress. Experiments were performed using isolated left ventricular cardiomyocytes from adult mice. Depletion and restoration of membrane cholesterol was achieved by applying methyl-β-cyclodextrin (MβCD) and water soluble cholesterol (WSC), respectively, and t-tubule remodeling in response to acute hyposmotic stress was assessed using fluorescent dextran trapping assay and by measuring t-tubule dependent IK1 tail current (IK1,tail). The amount of dextran trapped in t-tubules sealed in response to stress was significantly increased when compared to control cells, and reintroduction of cholesterol to cells treated with MβCD restored the amount of trapped dextran to control values. Alternatively, application of WSC to normal cells significantly reduced the amount of trapped dextran further suggesting the protective effect of cholesterol. Importantly, modulation of membrane cholesterol (without osmotic stress) led to significant changes in various parameters of IK1, tail strongly suggesting significant but essentially hidden remodeling of t-tubules prior to osmotic stress. Results of this study demonstrate that modulation of the level of membrane cholesterol has significant effects on the susceptibility of cardiac t-tubules to acute hyposmotic stress.

Leveraging the test effect to improve maintenance of the gains achieved through cognitive rehabilitation.

An important aspect of the rehabilitation of cognitive and linguistic function subsequent to brain injury is the maintenance of learning beyond the time of initial treatment. Such maintenance is often not satisfactorily achieved. Additional practice, or overtraining, may play a key role in long-term maintenance. In particular, the literature on learning in cognitively intact persons has suggested that it is testing, and not studying, that contributes to maintenance of learning. The present study investigates the hypothesis that continuing to test relearned words in persons with anomia will lead to significantly greater maintenance compared with continuing to study relearned words. The current study combines overtraining with the variable of test versus study in examining the effects of overtesting and overstudying on maintenance of word finding in 3 persons with aphasia. First, treatment successfully reestablished the connections between known items and their names. Once the connections were reestablished (i.e., items could be named successfully), each item was placed into 1 of 4 overtraining conditions: test and study, only test, only study, or no longer test or study. Maintenance was probed at 1 month and 4 months following the end of overtraining. The results are consistent with an advantage of testing compared with studying. All 3 participants showed significantly greater maintenance for words that were overtested than for words that were overstudied. This testing benefit persisted at 1 month and 4 months after completion of the treatment. In fact, there was no clear evidence for any benefit of overstudying. The present study demonstrates that overtesting, but not overstudying, leads to lasting maintenance of language rehabilitation gains in patients with anomia. The implications for the design of other treatment protocols are immense. (PsycINFO Database Record

Predictive ability of preinjury stressful life events and post-traumatic stress symptoms for outcomes following mild traumatic brain injury: analysis in a prospective emergency room sample

BackgroundA subset of persons with mild traumatic brain injury (mTBI) experience long-term difficulties. Preinjury stress has been hypothesised to play a role in long-term maintenance of symptoms.ObjectiveTo investigate the predictive...

The protein kinase Mζ network as a bistable switch to store neuronal memory

BackgroundProtein kinase Mζ (PKMζ), the brain-specific, atypical protein kinase C isoform, plays a key role in long-term maintenance of memory. This molecule is essential for long-term potentiation of the neuron and various modalities of learning such as spatial memory and fear conditioning. It is unknown, however, how PKMζ stores information for long periods of time despite molecular turnover.ResultsWe hypothesized that PKMζ forms a bistable switch because it appears to constitute a positive feedback loop (PKMζ induces its local synthesis) part of which is ultrasensitive (PKMζ stimulates its synthesis through dual pathways). To examine this hypothesis, we modeled the biochemical network of PKMζ with realistic kinetic parameters. Bifurcation analyses of the model showed that the system maintains either the up state or the down state according to previous inputs. Furthermore, the model was able to reproduce a variety of previous experimental results regarding synaptic plasticity and learning, which suggested that it captures the essential mechanism for neuronal memory. We proposed in vitro and in vivo experiments that would critically examine the validity of the model and illuminate the pivotal role of PKMζ in synaptic plasticity and learning.ConclusionsThis study revealed bistability of the PKMζ network and supported its pivotal role in long-term storage of memory.

The protein kinase Mζ network as a bistable switch to store neuronal memory

Protein kinase Mζ (PKMζ), the brain-specific, atypical protein kinase C isoform, plays a key role in long-term maintenance of memory. This molecule is essential for long-term potentiation of the neuron and various modalities of learning such as spatial memory and fear conditioning. It is unknown, however, how PKMζ stores information for long periods of time despite molecular turnover. We hypothesized that PKMζ forms a bistable switch because it appears to constitute a positive feedback loop (PKMζ induces its local synthesis) part of which is ultrasensitive (PKMζ stimulates its synthesis through dual pathways). To examine this hypothesis, we modeled the biochemical network of PKMζ with realistic kinetic parameters. Bifurcation analyses of the model showed that the system maintains either the up state or the down state according to previous inputs. Furthermore, the model was able to reproduce a variety of previous experimental results regarding synaptic plasticity and learning, which suggested that it captures the essential mechanism for neuronal memory. We proposed in vitro and in vivo experiments that would critically examine the validity of the model and illuminate the pivotal role of PKMζ in synaptic plasticity and learning. This study revealed bistability of the PKMζ network and supported its pivotal role in long-term storage of memory.

Hsp27 is persistently expressed in zebrafish skeletal and cardiac muscle tissues but dispensable for their morphogenesis

Constitutive expression of Hsp27 has been demonstrated in vertebrate embryos, especially in developing skeletal and cardiac muscle. Results of several previous studies have indicated that Hsp27 could play a role in the development of these tissues. For example, inhibition of Hsp27 expression has been reported to cause defective development of mammalian myoblasts in vitro and frog embryos in vivo. In contrast, transgenic mice lacking Hsp27 develop normally. Here, we examined the distribution of Hsp27 protein in developing and adult zebrafish and effects of suppressing Hsp27 expression using phosphorodiamidate morpholino oligonucleotides (PMO) on zebrafish development. Consistent with our previous analysis of hsp27 messenger RNA expression, we detected the protein Hsp27 in cardiac, smooth, and skeletal muscle of both embryonic and adult zebrafish. However, embryos lacking detectable Hsp27 after injection of antisense hsp27 PMO exhibited comparable heart beat rates to that of control embryos and cardiac morphology was indistinguishable in the presence or absence of Hsp27. Loss of Hsp27 also had no effect on the structure of the skeletal muscle myotomes in the developing embryo. Finally, embryos injected with antisense hsp27 and scrambled control PMO displayed equal motility. We conclude that Hsp27 is dispensable for zebrafish morphogenesis but could play a role in long-term maintenance of heart and muscle tissues.

IL-15 Regulates CD8+ T Cell Contraction during Primary Infection

During the course of acute infection with an intracellular pathogen, Ag-specific T cells proliferate in the expansion phase, and then most of the T cells die by apoptosis in the following contraction phase, but the few that survive become memory cells and persist for a long period of time. Although IL-15 is known to play an important role in long-term maintenance of memory CD8+ T cells, the potential roles of IL-15 in CD8+ T cell contraction are not known. Using an adoptive transfer system of OT-I cells expressing OVA257-264/Kb-specific TCR into control, IL-15 knockout (KO) and IL-15 transgenic (Tg) mice followed by challenge with recombinant Listeria monocytogenes expressing OVA, we found that the survival of CD44+CD62L-CD127- effector OT-I cells during the contraction phase is critically dependent on IL-15. In correlation with the expression level of Bcl-2 in OT-I cells, the number of OT-I cells was markedly reduced in IL-15 KO mice but remained at a high level in IL-15 Tg mice during the contraction phase, compared with control mice. In vivo administration of rIL-15 during the contraction phase in IL-15 KO mice inhibited the contraction of effector OT-I cells accompanied by up-regulation of Bcl-2 expression. Furthermore, enforced expression of Bcl-2 protected the majority of effector OT-I cells from death in IL-15 KO mice after infection. These results suggest that IL-15 plays a critical role in protecting effector CD8+ T cells from apoptosis during the contraction phase following a microbial infection via inducing antiapoptotic molecules.

Overexpression of IL-15 In Vivo Increases Antigen-Driven Memory CD8+ T Cells Following a Microbe Exposure

To elucidate potential roles of IL-15 in the maintenance of memory CD8+ T cells, we followed the fate of Ag-specific CD8+ T cells directly visualized with MHC class I tetramers coupled with listeriolysin O (LLO)(91-99) in IL-15 transgenic (Tg) mice after Listeria monocytogenes infection. The numbers of LLO(91-99)-positive memory CD8+ T cells were significantly higher at 3 and 6 wk after infection than those in non-Tg mice. The LLO(91-99)-positive CD8+ T cells produced IFN-gamma in response to LLO(91-99), and an adoptive transfer of CD8+ T cells from IL-15 Tg mice infected with L. monocytogenes conferred a higher level of resistance against L. monocytogenes in normal mice. The CD44+ CD8+ T cells from infected IL-15 Tg mice expressed the higher level of Bcl-2. Transferred CD44+ CD8+ T cells divided more vigorously in naive IL-15 Tg mice than in non-Tg mice. These results suggest that IL-15 plays an important role in long-term maintenance of Ag-specific memory CD8+ T cells following microbial exposure via promotion of cell survival and homeostatic proliferation.

Low Dose Interferon Alfa-2B for the Induction of Remission of Hairy Cell Leukemia: A Multi-institutional Study of 49 Patients.

This multicenter study reports on 49 patients with hairy cell leukemia (HCL) who were treated subcutaneously with alfa-2b interferon (Intron A, Schering Corporation, Kenilworth, N.J.), three times a week at a reduced dosage of 200,000 units/m(2), one-tenth the dose of the standard 2 million units/m(2). The response rate (normalized blood counts) was 22% (11 of 49); an additional 12 patients had a minor response for an overall response rate of 47% (23 of 49). When response was assessed by prior IFN therapy, no significant difference was noted. Five of 21 (24%) with no prior IFN and 6 of 28 (21%) with prior IFN therapy achieved at least a normalization of blood counts (p = 0.07). The response rate with low-dose interferon is inferior to that with standard dose interferon and should not be used for remission induction, but should be evaluated for its role in long-term maintenance of response.