Search PubMed⌕ Search

Biomedical subjects

C L Williams

Publications and source records attributed to C L Williams.

At least 73 records · Page 4Linked to original sources

Reactivation treatment prevents the memory-impairing effects of scopolamine in preweanling rats.

The authors report that the expression of a conditioned odor aversion is impaired in preweanling rats when they are conditioned on Postnatal Day 12 and tested under the influence of scopolamine hydrobromide (0.2 or 0.5 mg/kg, intraperitoneal) after a 48-hr, but not after a 2-hr, retention interval (Experiment 1). This effect of scopolamine is not dependent on maturation of the cholinergic system between Days 12 and 14 (Experiment 2), nor is it due to peripheral mechanisms (Experiment 3). When pups are reexposed to the unconditioned stimulus (footshock) before drug administration, performance on the 48-hr retention test is not impaired by scopolamine (Experiment 4). These findings demonstrate that the cholinergic system may be critical for the retrieval and expression of long-term or weak memories in young rats. However, the expression of active memories (recent or recently reactivated) may not be dependent on the cholinergic system to the same extent as is the expression of inactive memories.

Age Factors↗

Norepinephrine release in the amygdala after systemic injection of epinephrine or escapable footshock: contribution of the nucleus of the solitary tract.

Several findings based largely on lesions and drug manipulations within the amygdala suggest that norepinephrine (NE) systems in the amygdala contribute to enhancement of memory processes by epinephrine (EPI). However, no studies to date have directly measured changes in the release of NE in the amygdala after EPI injection. In Experiment 1, in vivo microdialysis was used to assess amygdala NE release after systemic injection of saline, EPI (0.1 or 0.3 mg/kg), and administration of an escapable footshock (0.8 mA, 1 s). Both doses of EPI produced a significant elevation in NE release that persisted for up to 60 min. In Experiment 2, the local anesthetic lidocaine (2%) was infused (0.5 microl) into the nucleus of the solitary tract (NTS) immediately before injection of 0.3 mg/kg EPI. The EPI-induced elevation in amygdala NE release observed in Experiment I was attenuated by inactivation of the NTS. These findings indicate that systemic injection of EPI increases release of NE in the amygdala and suggest that the effects are mediated in part by activation of brainstem neurons in the NTS that project to the amygdala.

Amygdala↗

Dietary fat consumption and health.

Dietary Guidelines have emerged over the past 30 years recommending that Americans limit their consumption of total fat and saturated fat as one way to reduce the risk of a range of chronic diseases. However, a low-fat diet is not a no-fat diet. Dietary fat clearly serves a number of essential functions. For example, maternal energy deficiency, possible exacerbated by very low-fat intakes (< 15% of energy), is one key determinant in the etiology of low birth weight. The debate continues over recommendations for limiting total fat and saturated fatty acid intake in children. Recent evidence indicates that diets with adequate energy providing less than 30% of energy from fat are sufficient to promote normal growth and normal sexual maturation. More attention needs to be devoted to the effect of dietary fat reduction on the nutrient density of children's diets. The association between dietary fat and CHD has been extensively studied. Diets high in saturated fatty acids and trans fatty acids increase LDL cholesterol levels, and in turn, the risk of heart disease. The relationship between high-carbohydrate/low-fat diets and CHD is more ambiguous because high-carbohydrate diets induce dyslipidemia in certain individuals. Obesity among adults and children is now of epidemic proportions in the United States. High-fat diets leading to excessive energy intakes are strongly linked to the increasing obesity in the United States. However, the prevalence of obesity has increased during the same time period that dietary fat intake (both in absolute terms and as a percentage of total dietary energy) has decreased. These trends suggest that a concomitant decrease in total dietary energy and modifications of other lifestyle factors, such as physical activity, also need to be emphasized. Obesity is also an independent risk factor for the development of diabetes. The current availability of fat-modified foods offers the potential for dietary fat reduction and treatment of the comorbidities associated with diabetes. However, to date, few studies have documented the effectiveness of fat-modified foods as part of a weight loss regimen or in reduction in CHD risks among individuals with diabetes mellitus. The association between total dietary fat and cancer is still under debate. While there is some evidence demonstrating associations between dietary fat intake and cancers of the breast, prostate, and colon, there are serious methodologic issues, including the difficulty in differentiating the effects of dietary fat independent of total energy intake. Reported total fat and saturated fatty acid intakes as a percentage of total energy have been declining over the past 30 years in the United States. Despite this encouraging trend, the majority of individuals--regardless of age--do not report consuming a diet that meets the levels of fat and saturated fatty acids recommended by the Dietary Guidelines for Americans. On a relative basis, saturated fat intake has gone down less than has total fat intake. Individuals of all ages who report consuming a diet with < or = 30% of energy from fat consistently have lower energy intakes. Given the increasing rates of obesity in the United States at an earlier and earlier age, dietary fat reduction may be an effective part of an overall strategy to balance energy consumption with energy needs. In each of the age/gender groups reporting consumption of < or = 30% of energy from fat and less than 10% of energy from saturated fatty acids, fat-modified foods play a more important role in their diets than for people who are consuming higher levels of fat and saturated fat. The data are clear than fat-modified foods make a more significant contribution to diets of consumers with low-fat intakes. While one cannot argue cause and effect from the results presented, the patterns of fat-modified foods/low-fat intakes are consistent. The focus on overall diet quality is often lost in the national obsession with lowering fat inta

Adult↗

Prenatal dietary choline supplementation decreases the threshold for induction of long-term potentiation in young adult rats.

Choline supplementation during gestation in rats leads to augmentation of spatial memory in adulthood. We hypothesized that prenatal (E12-E17) choline supplementation in the rat would lead to an enhancement of hippocampal synaptic plasticity as assessed by long-term potentiation (LTP) at 3-4 mo of age. LTP was assessed blindly in area CA1 of hippocampal slices with first suprathreshold (above threshold for LTP generation in control slices) theta-burst stimulus trains. The magnitude of potentiation after these stimuli was not different between slices from control and prenatally choline supplemented animals. Next, threshold (reliably leading to LTP generation in control slices) or subthreshold theta-burst stimulus trains were applied to slices from control, prenatally choline-supplemented, and prenatally choline-deprived rats. Threshold level stimulus trains induced LTP in slices from both the control and choline-supplemented rats but not in those from the choline-deficient rats. Subthreshold stimulus trains led to LTP induction in slices from prenatally choline-supplemented rats only. These observations indicate that prenatal dietary manipulation of the amino acid, choline, leads to subsequent significant alterations of LTP induction threshold in adult animals.

Animals↗

Regulation of integrin-mediated adhesion by muscarinic acetylcholine receptors and protein kinase C in small cell lung carcinoma.

STUDY OBJECTIVES: Improved understanding of the phenotypic characteristics of small cell lung cancer (SCLC) cells may facilitate the development of new therapies for this bronchogenic malignancy with early metastases. Herein we investigate whether activation of the M3 subtype of muscarinic acetylcholine receptor (mAChR) expressed on SCLC cells affects beta1-integrin-mediated adhesion of these cells. DESIGN: Adhesion of the SCLC cell lines SCC-9 and NCI-H345 to extracellular matrix (ECM) proteins was investigated. Cell adhesion was quantified by labeling the cells with either toluidine blue dye and measuring optical density or 3H-thymidine and measuring beta-activity. Fluorescence-activated cell sorting was used to quantify the SCLC cell surface expression of beta1-integrins. SETTING: Experiments were conducted in the Molecular Pharmacology Laboratory, Guthrie Research Institute. MEASUREMENTS AND RESULTS: Activation of mAChR with the agonist carbachol (10 microM, 1.5 h) significantly increases adhesion of the SCC-9 SCLC cell line to the ECM proteins laminin and collagen types I and IV. In contrast, mAChR activation does not alter the adhesion of SCC-9 cells to vitronectin, fibronectin, poly-L-lysine, or bovine serum albumin. Carbachol also does not alter the adhesion of NCI-H345 SCLC cells that lack functional mAChR. Preincubation of SCC-9 cells with the AIIB2 blocking antibody to beta1-integrin inhibits mAChR-induced adhesion to ECM proteins. Immunofluorescence analysis indicates that mAChR activation does not alter the surface expression of beta1-integrins by SCC-9 cells. Direct stimulation of protein kinase C (PKC) by treatment with phorbol 12-myristate 13-acetate (PMA) (10 nM, 1.5 h) increases the adhesion of both the SCC-9 and NCI-H345 cell lines to ECM proteins. These results indicate that direct activation of PKC or stimulation of M3 mAChR (which results in increased PKC activity) increases the binding activity of beta1-integrins, resulting in increased adhesion of SCLC cells to ECM proteins. CONCLUSIONS: The ability of mAChR to regulate SCLC proliferation and adhesion suggests that activation of these receptors may be used to alter SCLC tumorigenesis and metastasis.

Atropine↗

Longevity in age-heterogamous marriages.

A post facto analysis was conducted to study the relationship between longevity and age-heterogamous marriages with data from 776 cemetery records. A significant positive linear relationship was found between age difference and age at death of men. No significant relationship was found for women.

Age Factors↗

Severe morbid onychophagia: the classification as self-mutilation and a proposed model of maintenance.

OBJECTIVES: The aim of this review is to make a distinction between a mild and a severe form of onychophagia (nailbiting) that has not been adequately recognised in clinical research. Furthermore, the aim is to emphasise the need for greater understanding of the motivation for such self-injury as occurs in the severe form. The purpose of making the distinction is to evaluate whether a label of self-mutilation can be applied to the severe form. If this is the case, the tension-reduction model of self-mutilation can be proposed as the mechanism which may maintain the behaviour in the face of serious social and physical consequences. METHOD: Examination was made of the literature relating to onychophagia and to self-mutilation. Treatment studies of onychophagia were examined to evaluate the mechanisms by which the behaviour may be maintained. RESULTS: Considering the self-mutilative nature of the severe form and the common theme of tension reduction in the literature on onychophagia, application of the tension-reduction model of self-mutilation is warranted. CONCLUSION: There is a need for empirical research as to the tension-reducing nature of severe onychophagia.

Anxiety↗

Lessons from Project Northland: preventing alcohol problems during adolescence.

Project Northland, an ongoing community trial aimed at reducing alcohol use and alcohol-related problems among adolescents, is nearing completion. The project combines individual-based strategies to encourage adolescents not to use alcohol with community-based strategies to both reduce alcohol availability and modify community attitudes concerning youth drinking. Project Northland has developed prevention programs and followed the same group of adolescents from sixth grade to high school graduation. This article discusses the rationale for this type of program, elements of the adolescents' social environment targeted for change, the unique challenges of working with high school students compared with younger adolescents, and areas for future research.

Adolescent↗

Ethanol disrupts carbamylcholine-stimulated release of arachidonic acid from Chinese hamster ovary cells expressing different subtypes of human muscarinic receptor.

Ethanol disrupts signal transduction mediated by a variety of G-protein coupled receptors. We examined the effects of ethanol on arachidonic acid release mediated by muscarinic acetylcholine receptors. Chinese hamster ovary (CHO) cells transfected with the different subtypes of human muscarinic receptors (M1 to M5) were incubated with [3H]arachidonic acid ([3H]AA) for 18 hr, washed, and exposed to the cholinergic agonist carbamylcholine for 15 min. Carbamylcholine induced [3H]AA release from CHO cells expressing M1, M3, or M5, but not M2 or M4, muscarinic receptors. Dose response curves revealed that carbamylcholine stimulated [3H]AA release by up to 12-fold with an ECo of approximately 0.4 microM; maximal responses were obtained with 10 microM carbamylcholine. Exposure of M1-, M3-, or M5-expressing cells to ethanol for 5 min before stimulating with carbamylcholine reduced [3H]AA release by 40 to 65%; 50% of the maximal inhibition was obtained with an ethanol concentration of 30 to 50 mM. Ethanol did not affect basal [3H]AA release measured in the absence of carbamylcholine. Dose response curves suggest that ethanol acts as a noncompetitive inhibitor of muscarinic receptor-induced [3H]AA release insofar as maximal [3H]AA release was depressed in the presence of ethanol with no apparent change in the EC50 for stimulation by carbamylcholine. Exposure of CHO cells to 38 mM ethanol for 48 hr increased [3H]AA release induced by carbamylcholine without affecting basal [3H]AA release or altering the EC50 for carbamylcholine. These results indicate that ethanol acutely inhibits muscarinic receptor signaling through the arachidonic acid pathway in a noncompetitive manner, but chronically enhances muscarinic signaling through the same pathway.

Animals↗

Influence of acute and chronic ethanol treatment on muscarinic responses and receptor expression in Chinese hamster ovary cells.

The influence of ethanol on the muscarinic receptor-mediated release of inositol phosphate from Chinese hamster ovary (CHO) cells stably transfected with one of the five subtypes of muscarinic acetylcholine receptor was determined. In CHO cells expressing M3 muscarinic receptors (CHO-M3), carbamylcholine increased muscarinic receptor-induced release of inositol phosphate by 150-350% following a 15-min incubation with an EC50 of approximately 30 microM. Maximal responses were obtained with 1 mM carbamylcholine, while responses to 10 mM carbamylcholine were somewhat less than maximal. Preincubation with atropine for 10 min inhibited the response with an IC50 of approximately 30 nM. CHO cells transfected with M1, M3, and M5 receptors displayed a similar pattern of activity; CHO cells transfected with M2 and M4, as well as untransfected cells, were unresponsive to carbamylcholine. Ethanol acutely inhibited the response of CHO-M3 cells to carbamylcholine by 15% at 18 mM and by 47% at 180 mM (the highest concentration examined). CHO-M3 cells were incubated with 50 mM ethanol for 48 hr. This treatment did not affect the number of cells or their protein content (113 pg/cell). The expression of M3 muscarinic receptors (determined using [3H]N-methylscopolamine) increased from 1.34 +/- 0.23 to 1.75 +/- 0.16 pmol/mg protein (P < 0.05). In contrast, carbamylcholine-stimulated release of inositol phosphate was depressed by 40-70% in four experiments. Concentration-response analyses indicated a non-competitive inhibitory mechanism. This dissociation of muscarinic receptor expression and muscarinic signaling suggests a compensatory increase in receptor expression in response to chronic inhibition of muscarinic signaling by ethanol.

Animals↗

Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats.

Rats were trained at 2-4 months and at 24-26 months of age on a peak-interval timing procedure in which auditory and visual stimuli signaled two different fixed-interval schedules of reinforcement (15 and 30 s) that were presented simultaneously in a hierarchical fashion. Compared with control rats, increases in the probability of attention to the 15 s signal were observed for both the choline-supplemented and the choline-deficient rats. In contrast, an increase in attention to the 30 s signal was only observed for the choline-supplemented rats, whereas choline-deficient rats exhibited a decrease in attention that increased with age. Proportional rightward shifts in the remembered times of reinforcement emerged for the 24-26-month-old rats in the choline-deficient and control groups, but not in the choline-supplemented group. These results indicate that prenatal choline supplementation facilitates cognitive function across the lifespan, whereas prenatal choline deficiency impairs divided attention and accelerates age-related declines in temporal processing.

Acoustic Stimulation↗

Perinatal choline supplementation increases the threshold for chunking in spatial memory.

Chunking and perinatal choline supplementation each provide rats with alternative memory processing advantages. Evidence from radial-arm maze performance of adult (2- to 5-month-old) rats indicates that chunking of multiple food types (sunflower seeds, Noyes pellets and rice puffs) emerges for stable, differentiable baiting patterns as a function of the memory load (6, 12, 18 or 24 maze arms). The number of maze arms appeared to determine both the level of task difficulty at which rats began to implement a chunking strategy as well as when they were unable to successfully implement such a strategy due to the excess memorial demands of the task. In comparison to control rats, rats treated perinatally with choline supplementation displayed a horizontal rightward shift of the response function that related level of clustering of like-food types to the number of maze arms. These results indicate a higher threshold for implementing a chunking strategy in rats treated perinatally with choline supplementation, possibly due to a choline-induced increase in memory capacity.

Animals↗

Characterization of the facilitative effects of perinatal choline supplementation on timing and temporal memory.

Perinatal choline supplementation can improve performance on a variety of spatial memory tasks in adulthood. In order to extend these studies, we have investigated the effects of perinatal choline supplementation on the performance of a peak-interval timing task in which a 20 s temporal criterion was trained for a visual signal in adult (3-6 months old) rats. Following 5 weeks of baseline training, rats received systemic injections of nicotine (0.1, 0.2, or 0.4 mg/kg, s.c.) or saline prior to testing on the peak-interval timing task. The results indicated that perinatal choline supplementation increased rats' sensitivity to the 20 s temporal criterion during baseline training and facilitated the clock speed enhancing effects of nicotine during drug testing. The present study extends the types of long-term cognitive enhancement produced by perinatal choline supplementation to include the temporal processing domain and relates these effects to modifications in cholinergic function.

Analysis of Variance↗

Management of childhood obesity in pediatric practice.

Evaluation of obese children and adolescents in the pediatric office or clinic should include baseline assessment of weight for height and body fatness; rule out endocrine and genetic causes of obesity; and evaluate other health-risk factors, such as those for cardiovascular disease, cancer, diabetes, and hypertension. Treatment of obesity is most successful if realistic goals are set; a balanced low-fat/high-fiber diet is stressed; a safe rate of weight loss of 1 to 2 pounds per week is achieved through a moderate reduction of caloric intake (approximately 20-25% decrease); increased physical activity is stressed as much as diet; parental support is strong; and behavior therapy is provided during the course of treatment to help both child and parent achieve the diet, exercise, and behavior goals.

Adolescent↗

Regulation of cadherin-mediated adhesion by the small GTP-binding protein Rho in small cell lung carcinoma cells.

Metastasis is one of the most important factors responsible for the pathogenesis of small cell lung carcinoma (SCLC). SCLC cells express cadherins, which are homophilic cell-cell adhesion molecules that play an important role in the regulation of metastasis. We present the first evidence that altering the activity of the small GTP-binding protein Rho induces cadherin-mediated adhesion. ADP-ribosylation of Rho upon incubation or electroporation with recombinant C3 exoenzyme induces rapid aggregation and compaction of SCLC cells. Aggregation and compaction induced by C3 exoenzyme are diminished by removal of extracellular Ca2+ and by the HECD blocking antibody to E-cadherin but not by antibodies to other adhesion molecules. Altering the activity of Rho by ADP-ribosylation does not alter surface expression of E-cadherin, but it alters G actin content, as indicated by the binding of DNase I. Treatment with cytochalasin D also alters G actin content and increases aggregation and compaction of SCLC cells. These findings implicate Rho in the regulation of cadherin-mediated adhesion and identify Rho as a potential therapeutic target for the control of SCLC metastasis.

ADP Ribose Transferases↗

Inhibition of M3 muscarinic acetylcholine receptor-mediated Ca2+ influx and intracellular Ca2+ mobilization in neuroblastoma cells by the Ca2+/calmodulin-dependent protein kinase inhibitor 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-trosyl]-4-phenylpiperazin e (KN-62).

The role of Ca2+/calmodulin-dependent protein kinase (CaM kinase; EC 2.7.1.123) in the generation of Ca2+ signals by muscarinic acetylcholine receptors (mAChR) was studied. Changes in intracellular Ca2+ concentrations ([Ca2+]i) induced by mAChR activation were monitored in SK-N-SH human neuroblastoma cells using the dye Fura-2. SK-N-SH cells express M3 mAChR, as well as CaM kinase types II and IV, which are specifically inhibited by the CaM kinase antagonist KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne). Carbamylcholine (100 microM) elicited an initial transient peak in [Ca2+]i due to mobilization of Ca2+ from internal stores, followed by a sustained elevation in [Ca2+]i that depended on the influx of extracellular Ca2+ and which was inhibited by EGTA and Ni2+. These mAChR-induced Ca2+ signals were diminished to an equal extent by preincubating the cells with 0.01 to 100 microM KN-62. KN-62 inhibited mAChR-induced Ca2+ influx and mobilization from internal stores by about 25-30%, producing a half-maximal effect at approximately 1 microM. In contrast, KN-62 (25 microM) almost completely abolished carbamylcholine-stimulated entry of divalent cations through Mn2+-permeant channels, as revealed by Mn2+ quenching of Fura-2 fluorescence. KN-62 also almost completely abolished Ca2+ influx induced by depolarization of the cells with 25 mM K+ (IC50 = 3 microM). These results suggest that CaM kinases regulate both the mobilization of intracellular Ca2+ and the stimulation of Ca2+ influx that are induced by mAChR activation, and indicate that the mAChR-induced influx of Ca2+ occurs through Ca2+ channels other than, or in addition to, the voltage-gated calcium channels or Mn2+-permeant channels which are inhibited by KN-62.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Coping and problem solving of self-mutilators.

People who self-mutilate have been hypothesized to have deficient skills in coping and problem-solving that leave them vulnerable to the adoption of self-mutilation as a coping strategy. This hypothesis was tested using male incarcerated self-mutilators with comparisons being made with non-multilating, prisoner, and non-prisoner control groups. Examination of the inherent resources which enable an individual to effectively cope with stress demonstrated a depressed score for self-mutilators on the scale measuring self-worth and optimism about life. Assessment of the strategies used to cope with real problems demonstrated that self-mutilators engage in more problem avoidance behaviors. Self-mutilators also recorded less perceived control over problem-solving options. The results are discussed in terms of the effectiveness of self-mutilation as a coping strategy and the need to adopt a multidimensional approach to the investigation of coping.

Adaptation, Psychological↗