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Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 145 records · Page 8Linked to original sources

Human mesenchymal stem cells maintain transgene expression during expansion and differentiation.

Human adult bone marrow contains both hematopoietic stem cells that generate cells of all hematopoietic lineages and human mesenchymal stem cells (hMSCs), which support hematopoiesis and contribute to the regeneration of multiple connective tissues. The goal of the current study was to demonstrate that transduced hMSCs maintain transgene expression after stem cell differentiation in vitro and in vivo. We have introduced genes into cultured hMSCs by retroviral vector transfer and demonstrated long-term in vitro and in vivo expression of human interleukin 3 (hIL-3) and green fluorescent protein (GFP). Protocols were developed to achieve transduction efficiencies of 80-90% in these stem cells. In vitro expression of hIL-3 averaged 350 ng/10(6)cells/24 h over 17 passages (> 6 months) and GFP expression was stable over the same time period. Transduced hMSCs were able to differentiate into osteogenic, adipogenic, and chondrogenic lineages and maintained transgene expression after differentiation. Parallel studies were performed in vivo using NOD/SCID mice. Human MSCs expressing hIL-3 were cultured on several matrices and then delivered by subcutaneous, intravenous, and intraperitoneal routes. Sampling of peripheral blood demonstrated that systemic hIL-3 expression was maintained in the range of 100-800 pg/ml over a period of 3 months. These results illustrate the ability of hMSCs to express genes of therapeutic potential and demonstrate their potential clinical utility as cellular vehicles for systemic gene delivery.

Adult↗

Failure of endothelin-1 to activate store-operated Ca2+ channels by lack of mobilization from intracellular Ca2+ stores in cultured bovine adrenal chromaffin cells.

We have recently shown that in addition to L-type voltage-operated Ca2+ channel (VOC), endothelin-1 (ET-1) stimulation opens two types of Ca2+-permeable nonselective cation channels [designated nonselective cation channel-1 (NSCC-1) and NSCC-2]. However, in this Ca2+ entry, the involvement of store-operated Ca2+ channel (SOCC), which is suggested to exist in chromaffin cells, was unclear. Those NSCCs as well as SOCC can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. To clarify whether SOCC should actually exist and play a role in Ca2+ entry in chromaffin cells stimulated with ET-1, we examined the effects of removal of extracellular Ca2+, thapsigargin (TG, an inhibitor of endoplasmic reticulum Ca2+-ATPase), LOE 908 and SK&F 96365 on cytosolic free Ca2+ concentrations ([Ca2+]i) in cultured bovine adrenal chromaffin cells. After the cells were exposed to Ca2+-free medium followed by exposure to TG to deplete Ca2+ from the intracellular Ca2+ store, restoration of extracellular Ca2+ caused a gradual increase in [Ca2+]i (to about 200% of control). The increase was unaffected by LOE 908, but completely abolished by SK&F 96365. In the Ca2+-free medium, no increase in [Ca2+]i by ET-1 was observed, but the subsequent restoration of extracellular Ca2+ induced a rapid increase in [Ca2+]i (to the same level of [Ca2+]i as that evoked by ET-1 in the normal medium (1.0 mM Ca2+)). Since SK&F 96365 is also a blocker of SOCC, these results indicate that in bovine adrenal chromaffin cells, Ca2+ entry through SOCC (Ca2+ influx through the capacitative Ca2+ entry system) occurs but is comparably weak, and that it virtually does not work on the stimulation of ET-1.

Acetamides↗

Increased incidence of dyskinesias and other behavioral effects of re-exposure to neuroleptic treatment in social colonies of Cebus apella monkeys.

RATIONALE: Typical neuroleptic medications are still administered to as many as 40% of patients receiving antipsychotic treatment in the US. Intermittent administration or interruption of long-term neuroleptic medication for schizophrenia may increase the incidence of human tardive dyskinesias, and similarly may produce increasingly marked motor side-effects, parkinsonism, and other behavioral pathologies in non-human primates. OBJECTIVES AND METHODS: Given these similarities, we addressed the issue of prolonged and intermittent typical neuroleptic treatment and dopaminergic function during a 5-year, multi-phase study with social colonies of Cebus apella monkeys. In the previously reported phase 1, we examined the effects of 48 weeks of exposure to, followed by withdrawal from, fluphenazine decanoate (FPZ). Phase 3 reported here examined the effects of 18 weeks of re-exposure to FPZ in these same monkeys, 91 weeks after discontinuation of their phase 1 FPZ treatment. RESULTS: Analysis of blood plasma FPZ indicated levels of 0.22+/-0.08 ng/ml for the six injections during the re-exposure period (n=54), comparable to the 0.24+/-0.07 ng/ml levels measured during our original treatment with this dose. Acute dyskinesias and dystonias increased by 300% upon re-exposure to FPZ; 15 of 18 FPZ-treated animals exhibited oral-buccal dyskinesias and all exhibited torticollis or retrocollis. Retreatment with FPZ was also associated with highly significant reductions in Self- and Environment-Directed Behavior and Directed Affiliation, effects similar to those seen during the original phase 1 FPZ treatment. Although FPZ re-treatment was associated with a significant reduction in Directed Aggression (an effect that was more robust than that observed during phase 1), in phase 3, we again observed an increase in Directed Aggression during early drug discontinuation when animals were in a stress-inducing situation. CONCLUSIONS: These results both support our phase 1 conclusion that typical neuroleptic medications may contribute to negative symptoms of schizophrenia and provide additional evidence for the possibility of increased aggression in stressful situations when medication is discontinued. Additionally, the results indicate that intermittent treatment with typical neuroleptics may dramatically increase the incidence of dystonias and dyskinesias.

Aggression↗

Unique properties of four lactobacilli in amino acid production and symbiotic mixed culture for lactic acid biosynthesis.

With four Lactobacilli--L. delbrueckii subsp. lactis (ATCC 12315), L. casei (NRRL-B1445), L. delbrueckii (NRRL-B445), and L. heveticus (NRRL-B1937)--the characteristics of cell growth and production of lactate and amino acids were investigated. Especially, the time-course variation in concentration of amino acids (classified into alanine, serine, aspartate, glutamate, aromatic amino acid, and histidine families) was estimated in detail, and the results were systematically compared. It was elucidated that L. delbrueckii (NRRL-B445) and L. helveticus (NRRL-B1937) had quite different characteristics in growth, lactic acid synthesis, and amino acid production. L. helveticus (NRRL-B1937) was superior in the production of amino acids as well as in cell growth, but showed very poor ability in lactic acid production. However, L. delbrueckii (NRRL-B445) showed higher yield of lactic acid despite repressed cell growth, but suffered from severe amino acid deficiency in culture. By modulating the initial concentration of each strain in the mixed culture containing both L. delbrueckii (NRRL-B445) and L. helveticus (NRRL-B1937), the lactic acid production (i.e., the amount of lactic acid produced and lactic acid yield to glucose consumed) was significantly improved, presumably via symbiotic interaction between the two strains.

Amino Acids↗

Tissue distribution and functional expression of the human voltage-gated sodium channel beta3 subunit.

This study investigated the distribution of beta3 in human tissues and the functional effects of the human beta3 subunit on the gating properties of brain and skeletal muscle alpha subunits. Using RT-PCR of human cDNA panels, beta3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both alphaIIA and SkM1 expressed in Xenopus oocytes inactivated with a time course described by two exponential components representing fast and slow gating modes, while co-expression of human beta3 with alphaIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of beta3 a greater proportion of alphaIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. beta3 caused a hyperpolarizing shift in the voltage dependence of inactivation of alphaIIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with beta3 was described by a single Boltzmann equation similar to one of the Boltzmann components for SkM1 expressed alone, with a small positive shift in V1/2 value and reduced slope factor. This is the first study demonstrating that beta3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle alpha subunit, SkM1.

Amino Acid Sequence↗

The emergence of erythromycin-resistant Streptococcus pyogenes in Seoul, Korea.

High frequencies of erythromycin-resistant streptococci were reported in Japan in the mid-1970s, and in Finland in the late 1980s, related to an increase in the consumption of macrolide antibiotics in these countries. The frequency of erythromycin-resistant Streptococcus pyogenes was reported to be only 2% in 1994, but we know that the susceptibility of the strains to antibiotics had not been tested routinely. We studied the resistance rates of Streptococcus pyogenes to various antibiotics in Seoul, Korea, where antibiotics could be purchased without prescription. From January through December, 1998, 92 isolates of group A streptococci were collected from inpatients and outpatients with pharyngotonsillitis or invasive streptococcal infections, from institutions in five different geographic areas of Seoul; one pediatric clinic, three university hospitals, and one general hospital. All isolates were serotyped by T-agglutination, and minimum inhibitory concentrations (MICs) were determined by agar dilution methods, according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS). The most common T-serotype was T12 (44.6%), followed by T4 (19.6%). All the isolates tested were susceptible to penicillin, vancomycin, and cefotaxime. However, 38 isolates (41.3%) were resistant to erythromycin, 32 (34.8%) were resistant to clindamycin, and 48 (52.1%) were resistant to tetracycline. Twenty-seven of 41 isolates serotyped T12 and 3 of 18 isolates serotyped T28 were multiresistant to erythromycin, clindamycin, and tetracycline. Almost half of the isolates obtained from the five different areas in Seoul showed erythromycin resistance in Streptococcus pyogenes. Routine monitoring of antibiotic susceptibility tests and further extensive nationwide surveys are needed to determine the frequency and the extent of the spread of resistant strains in various geographic regions in Korea.

Adolescent↗

Umbilical cord serum ionized magnesium level and total pediatric mortality.

OBJECTIVE: To estimate whether higher magnesium levels in umbilical cord blood at delivery are associated with increased total pediatric (fetal + neonatal + postneonatal) mortality. METHODS: During the Magnesium and Neurologic Endpoints Trial, in addition to randomizing mothers having preterm labor into arms containing magnesium sulfate, other tocolytic agents, or saline controls, we obtained biologic specimens at delivery, including umbilical cord venous blood on which was determined the serum ionized magnesium level using the AVL 988-4 analyzer (Graz, Austria). Laboratory results were then matched with the pediatric mortalities. The study power was based on the anticipated reductions in neonatal intraventricular hemorrhage related to magnesium usage from 18.9% to 4.4%. For alpha =.05, 1-beta (power)=80%, two tailed, the total number of infants needed would be 140. RESULTS: Of 149 mothers who gave permission for randomization, ionized magnesium levels were available for 82 children. Seven deaths occurred (one immediately before delivery, three as neonates, and three in the postneonatal period). The median level of ionized magnesium among the seven dead children was 0.76 mmol/L; among the 75 survivors, the median level of ionized magnesium was 0.55 mmol/L (Mann-Whitney U test, P =.03). Using multivariable logistic regression analysis, the association remained statistically significant when controlling for possible confounding factors (adjusted odds ratio 7.7, 95% confidence interval 1.2, 47.6, P =.03). CONCLUSION: These findings of a dose response between serum ionized magnesium and deaths in children increase our concern about the improper use of tocolytic magnesium.

Adult↗

Infant mortality from congenital malformations in the United States, 1970-1997.

OBJECTIVE: We examined a trend in infant mortality caused by congenital malformations in the United States, particularly for the racial disparity between whites and nonwhites. METHODS: We used US annual summary data on cause-specific infant mortality for 1970-97 and detailed birth and infant death linked data for 1985-87, 1989-91, and 1995-97. RESULTS: Congenital malformations became a more prominent cause of infant mortality in 1997 and accounted for 22.1% of all infant deaths compared with 15.1% in 1970. Congenital malformations of nervous, cardiovascular, and respiratory systems accounted for more than 60% of all malformation deaths. Malformations incompatible with life (anencephaly, encephalocele, hypoplastic lungs, renal agenesis, and trisomies 13 and 18) were the cause of one-third of all malformation deaths. In 1970-71, infant mortality caused by congenital malformations in nonwhites was lower, 2.6 (confidence interval [CI] 2.5, 2.7) per 1000, compared with whites, 3.1 (CI 3.0, 3.1) per 1000. However, in 1996-97, the rate of congenital malformation-specific infant mortality was higher in nonwhites, 1.7 (CI 1.7, 1.8) per 1000, compared with whites, 1.6 (CI 1.5, 1.6) per 1000. This trend was most pronounced with central nervous system malformations. Although whites had an almost two-fold higher infant mortality rate from central nervous system malformations compared with nonwhites in 1970-71, this disparity was no longer present by 1996-97. CONCLUSION: Congenital malformations have become a leading cause of infant mortality in the 1990s. Over the last several decades, this mortality declined more slowly in nonwhites than in whites.

Congenital Abnormalities↗

STATT: a titrate-to-goal study of simvastatin in Asian patients with coronary heart disease. Simvastatin Treats Asians to Target.

BACKGROUND: Most published studies on the use of lipid-lowering agents to treat hypercholesterolemia have focused on Western populations, with few data on Asian populations. OBJECTIVE: The Simvastatin Treats Asians to Target (STATT) study used a titrate-to-goal protocol to evaluate the efficacy and tolerability of simvastatin 20 to 80 mg/d in the treatment of Asian patients with coronary heart disease. METHODS: This was a multicenter, open-label, uncontrolled, 14-week study in patients with coronary heart disease and serum low-density lipoprotein cholesterol (LDL-C) levels of 115-180 mg/dL and triglyceride levels of < or = 400 mg/dL. The dose of simvastatin was titrated from 20 to 80 mg/d to achieve the National Cholesterol Education Program (NCEP) LDL-C target of < or = 100 mg/dL. The primary efficacy measure was the percentage of patients achieving the NCEP target. Among secondary measures were the percentage of patients achieving European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension target LDL-C levels of < or = 115 mg/dL and the percentage change from baseline in lipid parameters. Tolerability was assessed in terms of the overall incidence of adverse experiences and the incidences of the most commonly reported adverse experiences. RESULTS: The intent-to-treat analysis included 133 Asian patients (93 men, 40 women; mean age, 59.5 years), of whom 125 completed 14 weeks of therapy. Their mean blood pressure was 130.2/79.4 mm Hg. Overall, 104 (78.2%) patients treated with simvastatin achieved LDL-C levels < or = 100 mg/dL at week 14, and 125 (94.0%) achieved this target at some point during the study. Similarly, 122 (91.7%) patients achieved an LDL-C level < or = 115 mg/dL at week 14, and 130 (97.7%) achieved this target at some point during the study. Treatment with simvastatin had favorable effects on the lipid profile, producing significant percentage changes from baseline in all parameters (P < 0.001). Simvastatin was well tolerated across the dose range. Overall, 40 patients (30.1%) had > or = 1 clinical adverse experience. Only 14 (10.5%) had adverse experiences that were possibly, probably, or definitely related to study drug; none of these experiences were considered serious. The most common adverse experiences (> or = 3% incidence) were abdominal pain (6%); chest pain (5%); dizziness (4%); and asthenia/fatigue, fibromyalgia, headache, insomnia, and upper respiratory tract infection (3% each). No new or unexpected adverse experiences were seen at the higher doses. CONCLUSIONS: Simvastatin was effective and well tolerated at doses of 20, 40, and 80 mg/d in Asian patients with coronary heart disease. Titration enabled the majority to achieve target LDL-C levels of < or = 100 mg/dL.

Aged↗

Factors affecting the forward shift of posterior corneal surface after laser in situ keratomileusis.

PURPOSE: To evaluate the anteroposterior movement of the corneal back surface after laser in situ keratomileusis (LASIK). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: One hundred ninety-six eyes of 120 subjects with myopic refractive errors of -2.0 to -12.5 diopters. INTERVENTION: LASIK was performed. Corneal topography of the posterior corneal surface was obtained with the scanning slit topography system before and 1 month after surgery. MAIN OUTCOME MEASURES: The amount of forward shift of the posterior corneal surface was determined. Multiple regression analysis was used to assess the factors that affect the forward shift of the posterior corneal surface. RESULTS: After surgery, the posterior corneal surface displayed mean forward shift of 40.9 +/- 24.8 micrometer. Explanatory variables relevant to the forward shift of corneal posterior surface were, in the order of magnitude of influence, the amount of laser ablation (partial regression coefficient B = 0.561, P < 0.0001), preoperative corneal thickness (B = -0.176, P = 0.00096), and preoperative intraocular pressure (B = 1.676, P = 0.0053). Preoperative refraction and achieved myopic correction showed collinearity with the amount of laser ablation. CONCLUSIONS: LASIK induces a forward shift of the cornea. Eyes with thinner corneas, higher intraocular pressure, and higher myopia requiring greater laser ablation are more predisposed to the anterior shift of the cornea.

Adult↗

cAMP potentiates H(2)O(2)-induced ERK1/2 phosphorylation without the requirement for MEK1/2 phosphorylation.

In Jurkat T lymphocytes, hydrogen peroxide (H(2)O(2)) potentiates the phosphorylation level of extracellular signal-regulated kinase 1 and 2 (ERK1/2) caused by T cell receptor (TCR) stimulation with anti-CD3 and anti-CD28 or anti-CD3 alone. Submillimolar concentrations of H(2)O(2)-induced phosphorylation of ERK1/2 and MAP/ERK kinase 1 and 2 (MEK1/2) without antigenic stimulation. H(2)O(2) also induced the electrophoretic mobility shift of Lck from 56 to 60 kDa. The MEK inhibitor, PD98059 attenuated ERK1/2 and MEK1/2 phosphorylation, as well as the migration shift of Lck induced by H(2)O(2). The phospholipase C (PLC) inhibitor, U73122, and EGTA reduced the phosphorylation of both ERK1/2 and MEK1/2 induced by H(2)O(2). Interestingly, an increase of intracellular cAMP level with forskolin or 8-(4-chlorophenylthio)-cAMP augmented ERK1/2 phosphorylation by H(2)O(2), while inhibiting MEK1/2 phosphorylation by H(2)O(2). These results demonstrate an alternative pathway that results in augmentation of ERK1/2 phosphorylation without concomitant MEK1/2 phosphorylation in T cells.

Colforsin↗

Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues.

New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a--d and 7a--d, were efficiently synthesized from the readily available starting materials, 1a--d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2--3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12--16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a--d and 7a--d. In the enzyme assay, however, the in vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of co-planarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100--200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety.

3',5'-Cyclic-GMP Phosphodiesterases↗

Pregnancy outcomes among U.S. Gulf War veterans: a population-based survey of 30,000 veterans.

PURPOSE: We evaluated an association between veterans' Gulf War service and reported adverse pregnancy outcomes. METHODS: We conducted a health survey in which selected reproductive outcomes of a population-based sample of 15,000 Gulf War veterans representing four military branches and three unit components (active, reserve, and National Guard) were compared to those of 15,000 non-Gulf veteran controls. RESULTS: Male Gulf veterans, compared with their non-Gulf veteran controls, reported a significantly higher rate of miscarriage (odds ratio [OR] = 1.62; 95% confidence interval [CI] = 1.32-1.99). Female Gulf veterans also reported more miscarriages than their respective controls, although their excess was not statistically significant (OR= 1.35; CI = 0.97-1.89). Both men and women deployed to the Gulf theater reported significant excesses of birth defects among their liveborn infants. These excess rates also extended to the subset of "moderate to severe" birth defects [males: OR= 1.78 (CI = 1.19-2.66); females: OR = 2.80 (CI = 1.26-6.25)]. No statistically significant differences by deployment status were found among men or women for stillbirths, pre-term deliveries or infant mortality. CONCLUSION: The risk of veterans reporting birth defects among their children was significantly associated with veteran's military service in the Gulf War. This observation needs to be confirmed by a review of medical records to rule out possible reporting bias.

Abortion, Spontaneous↗

Acute pancreatitis and bacterial translocation.

Infectious complications are the most frequent and severe complications of acute narcotizing pancreatitis (AP) with a mortality rate up to 80%. Although experimental and clinical studies suggest that the microbiologic source of pancreatic infection could be enteric, information in this regard is scant. This study evaluated bacterial translocation (BT) using mild and severe models of AP. Mild AP was induced by 6-hr continuous intravenous infusion of cerulein, while severe AP was induced by additional infusion of glycodeoxycholic acid into the biliopancreatic duct. BT was evaluated with organ cultures performed when animals were killed (24 hr). To confirm the gastrointestinal origin of the translocating microorganisms, fluorescent microspheres were also given to the animals in drinking water 24 hr before induction of AP. At the time of death beads were counted with a (fluorescence-activated cell sorter) (FACS) in peritoneal lavages and with fluorescent microscopy in frozen sections of the pancreata. Morphology of the distal small bowel showed significant changes in the animals with AP compared to controls, such as reduction of villus high and altered microvasculature. Mild AP induced BT to the pancreas in 100% of the animals, compared to pancreata from control groups. Severe AP induced increased BT to the pancreas. BT to liver and spleen was also significantly increased with AP. The presence of fluorescent microspheres confirmed their enteric derivation. This study provides evidence for the enteric origin of microorganisms responsible for pancreatic infectious complications during AP. The evidence of BT after laparotomy suggests an increased risk of infections with the association of these conditions. This could provide an explanation for the high mortality associated with laparotomy in course of AP.

Animals↗

MRP subfamily transporters and resistance to anticancer agents.

The MRP subfamily of ABC transporters from mammals consists of at least seven members, six of which have been implicated in the transport of amphipathic anions. MRP1, MRP2, and MRP3 bear a close structural resemblance, confer resistance to a variety of natural products as well as methotrexate, and have the facility for transporting glutathione and glucuronate conjugates. MRP1 is a ubiquitously expressed efflux pump for the products of phase II of xenobiotic detoxification, while MRP2, whose hereditary deficiency results in Dubin-Johnson syndrome, functions to extrude organic anions into the bile. MRP3 is distinguished by its capacity to transport the monoanionic bile constituent glycocholate, and may function as a basolateral back-up system for the detoxification of hepatocytes when the usual canalicular route is impaired by cholestatic conditions. MRP4 and MRP5 resemble each other more closely than they resemble MRPs 1-3 and confer resistance to purine and nucleotide analogs which are either inherently anionic, as in the case of the anti-AIDS drug PMEA, or are phosphorylated and converted to anionic amphiphiles in the cell, as in the case of 6-MP. Given their capacity for transporting cyclic nucleotides, MRP4 and MRP5 have also been implicated in a broad range of cellular signaling processes. The drug resistance activity and physiological substrates of MRP6 are unknown. However, its hereditary deficiency results in pseudoxanthoma elasticum, a multisystem disorder affecting skin, eyes, and blood vessels. It is hoped that elucidation of the resistance profiles and physiological functions of the different members of the MRP subfamily will provide new insights into the molecular basis of clinical drug resistance and spawn new strategies for combating this phenomenon.

Amino Acids↗

The influence of symbolic literacy on memory: testing Plato's hypothesis.

The present study examined the influence of the production of external symbols on memory strategies. Plato hypothesized that dependency on writing as an external memory store would be deterimental to memory. Three experiments were conducted to explore this hypothesis. Participants played Concentration, a memory game where players must find matching pairs of cards placed face down in an array. Participants were allowed to make notes to aid their performance under some experimental conditions, while under other conditions they could not. In Experiments 1 and 2, the unexpected removal of participants' notes revealed that the performance benefit was due to notes acting as a form of external memory storage, rather than as an aid to encoding information in memory. Experiment 3 qualified these findings by demonstrating that the identity of each card was retained in memory, while the location of each card tended to be stored in the participants' external notations. These data suggest a modified interpretation of Plato's hypothesis in that symbolic literacy may change how we remember information. Rather than storing all information in memory, we only have to retain the information necessary to use the much larger storage capacity of the external system. Thus, the introduction of external symbols allows for a change in how memory is adaptively distributed.

Adult↗

Effects of bisphosphonate on the remodeling of rat sagittal suture after rapid expansion.

The purpose of this study was to investigate the effects of bisphosphonate (BP), an inhibitor of bone resorption, on the remodeling of the rat sagittal suture after rapid expansion. Wistar strain male rats were divided into 4 groups and subjected to rapid mechanical expansion with an initial force of 60 g for 3 days. Immediately after the sutural expansion, the appliance was removed in 2 of the groups. In the S group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the B group, half of the animals were injected with bisphosphonate daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The remaining 2 groups underwent 7 days of mechanical retention before the appliance was removed. In the SR group, half of the animals were injected with saline solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. In the BR group, half of the animals were injected with bisphosphonate solution daily for 3 days and the other half were injected daily for 7 days prior to sacrifice. The calvariae were fixed in 4% neutral formalin, decalcified, and embedded in paraffin. The amount of relapse and the relevant bone remodeling were evaluated in terms of a relapse ratio and the number of osteoclasts. The relapse ratio was 54.11% in the S group and 32.53% in the B group 7 days after the injection. This ratio was 25.13% in the SR group and 9.60% in the BR group. The number of osteoclasts 3 days after injection was 15.47 in the S group, which was significantly greater than the 5.26 present in the B group. This number was 7.08 in the SR group, which was significantly greater than the 1.83 in the BR group. These results demonstrate that the injection of BP after rapid expansion, if combined with mechanical retention, may produce more secure retention by inhibiting bone resorption, indicating a possibility of employing a pharmaceutical aid to decrease the skeletal relapse after mechanotherapy in clinical orthodontics.

Acid Phosphatase↗