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1.
J Fish Biol ; 88(6): 2157-74, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27126719

ABSTRACT

To study growth rates, movements and estimate population size of shortfin eels Anguilla australis in a small lake (2·5 ha) near Christchurch, New Zealand, 617 A. australis were tagged with PIT tags. Tag retention was high (95%) and over the seven recapture events spread over 2 years, 55% of tagged A. australis were recaptured. Growth of recaptured A. australis averaged 13·1 mm year(-1) and declined slightly with increasing total length. Distance moved from original capture site increased with increasing time at large. Population estimates of A. australis > 400 mm (susceptible to capture by fyke net) from recaptures of individuals averaged 1451 A. australis, with a biomass of 170 kg ha(-1) . An average of 6·6% of the estimated total population matured as male silver A. australis each year. Results from radio-tracking of four A. australis gave an average nightly foraging area of 2780 m(2) , and there was no apparent preference for inshore movement (within 5-6 m of the shoreline) or offshore movement. Fyke-net efficiency (total catch relative to the estimated total population available to each net) measured over four consecutive nights fishing was 88%. The lack of precision of the shoreline triangulation system used, ±10 m, meant that the positional data were considered too coarse to be used in a proposed novel population estimation technique based on determining population size within foraging areas.


Subject(s)
Anguilla/physiology , Animal Distribution , Behavior, Animal , Lakes , Anguilla/growth & development , Animals , Biomass , Male , New Zealand , Population Density
2.
Mol Psychiatry ; 19(9): 1010-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24322204

ABSTRACT

Bipolar disorder (BD) is associated with higher body mass index (BMI) and increased metabolic comorbidity. Considering the associated phenotypic traits in genetic studies of complex diseases, either by adjusting for covariates or by investigating interactions between genetic variants and covariates, may help to uncover the missing heritability. However, obesity-related traits have not been incorporated in prior genome-wide analyses of BD as covariates or potential interacting factors. To investigate the genetic factors underlying BD while considering BMI, we conducted genome-wide analyses using data from the Genetic Association Information Network BD study. We analyzed 729,454 genotyped single-nucleotide polymorphism (SNP) markers on 388 European-American BD cases and 1020 healthy controls with available data for maximum BMI. We performed genome-wide association analyses of the genetic effects while accounting for the effect of maximum BMI, and also evaluated SNP-BMI interactions. A joint test of main and interaction effects demonstrated significant evidence of association at the genome-wide level with rs12772424 in an intron of TCF7L2 (P=2.85E-8). This SNP exhibited interaction effects, indicating that the bipolar susceptibility risk of this SNP is dependent on BMI. TCF7L2 codes for the transcription factor TCF/LF, part of the Wnt canonical pathway, and is one of the strongest genetic risk variants for type 2 diabetes (T2D). This is consistent with BD pathophysiology, as the Wnt pathway has crucial implications in neurodevelopment, neurogenesis and neuroplasticity, and is involved in the mechanisms of action of BD and depression treatments. We hypothesize that genetic risk for BD is BMI dependent, possibly related to common genetic risk with T2D.


Subject(s)
Bipolar Disorder/genetics , Bipolar Disorder/physiopathology , Body Mass Index , Polymorphism, Single Nucleotide , Transcription Factor 7-Like 2 Protein/genetics , Black or African American/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Logistic Models , Surveys and Questionnaires , White People/genetics
3.
Mol Psychiatry ; 19(6): 724-32, 2014 Jun.
Article in English | MEDLINE | ID: mdl-23999524

ABSTRACT

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition.


Subject(s)
Anorexia Nervosa/genetics , Epoxide Hydrolases/genetics , Genetic Variation , Adult , Anorexia Nervosa/metabolism , Body Mass Index , Case-Control Studies , Cholesterol/metabolism , Cohort Studies , Female , Genetic Predisposition to Disease , Humans , Longitudinal Studies , Male , Middle Aged , Polymorphism, Single Nucleotide , Psychometrics , White People/genetics , Young Adult
4.
Psychol Med ; 44(3): 543-53, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23701891

ABSTRACT

BACKGROUND: The purpose of this investigation was to compare a new psychotherapy for bulimia nervosa (BN), integrative cognitive-affective therapy (ICAT), with an established treatment, 'enhanced' cognitive-behavioral therapy (CBT-E). METHOD: Eighty adults with symptoms of BN were randomized to ICAT or CBT-E for 21 sessions over 19 weeks. Bulimic symptoms, measured by the Eating Disorder Examination (EDE), were assessed at baseline, at the end of treatment (EOT) and at the 4-month follow-up. Treatment outcome, measured by binge eating frequency, purging frequency, global eating disorder severity, emotion regulation, self-oriented cognition, depression, anxiety and self-esteem, was determined using generalized estimating equations (GEEs), logistic regression and a general linear model (intent-to-treat). RESULTS: Both treatments were associated with significant improvement in bulimic symptoms and in all measures of outcome, and no statistically significant differences were observed between the two conditions at EOT or follow-up. Intent-to-treat abstinence rates for ICAT (37.5% at EOT, 32.5% at follow-up) and CBT-E (22.5% at both EOT and follow-up) were not significantly different. CONCLUSIONS: ICAT was associated with significant improvements in bulimic and associated symptoms that did not differ from those obtained with CBT-E. This initial randomized controlled trial of a new individual psychotherapy for BN suggests that targeting emotion and self-oriented cognition in the context of nutritional rehabilitation may be efficacious and worthy of further study.


Subject(s)
Adaptation, Psychological , Bulimia Nervosa/therapy , Cognitive Behavioral Therapy/methods , Emotions , Models, Statistical , Self Concept , Adult , Anxiety/complications , Anxiety/psychology , Bulimia/psychology , Bulimia/therapy , Bulimia Nervosa/complications , Bulimia Nervosa/psychology , Depression/complications , Depression/psychology , Evidence-Based Practice , Female , Humans , Intention to Treat Analysis/statistics & numerical data , Interpersonal Relations , Interview, Psychological , Male , Models, Psychological , Motivational Interviewing , Outcome Assessment, Health Care/statistics & numerical data , Patient Education as Topic/methods , Severity of Illness Index , Surveys and Questionnaires
5.
J Ind Microbiol Biotechnol ; 38(9): 1567-73, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21409422

ABSTRACT

Despite the use of refrigeration, improved packaging, adsorbents, and ethylene receptor blockers, on average, nearly 40% of all fruits and vegetables harvested in the US are not consumed. Many plant products, especially fruit, continue to ripen after harvesting, and as they do so, become increasingly susceptible to mechanical injury, resulting in increased rot. Other plant products during transportation and storage are susceptible to chill injury (CI). There is a real need for products that can delay ripening or mitigate the effects of CI, yet still permit full ripeness and quality to be achieved. Preliminary results are discussed where catalyst derived from cells of Rhodococcus rhodochrous DAP 96253, grown under conditions that induced high levels of nitrile hydratase, were able to extend the ripening and thus the shelf-life of selected climacteric fruits (banana, avocado, and peach). A catalyst, when placed in proximity to, but not touching, the test fruit delayed the ripening but did not alter the final ripeness of the fruit tested. Organoleptic evaluations conducted with control peaches and with peaches exposed to, but not in contact with, the catalyst showed that the catalyst-treated peaches achieved full, natural levels of ripeness with respect to aroma, flavor, sweetness, and juice content. Furthermore, the results of delayed ripening were achieved at ambient temperatures (without the need for refrigeration).


Subject(s)
Fruit , Hydro-Lyases/metabolism , Rhodococcus/enzymology , Catalysis , Musa , Persea , Prunus
6.
Eat Weight Disord ; 16(4): e236-41, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22526129

ABSTRACT

Although previous research has supported the importance of anxiety as an etiological and maintenance factor for eating disorders, the specific mechanisms are not well understood. The role of anxiety in the context of eating behavior is especially unclear. The purpose of this study was to identify anxiety-eliciting eating situations and anxiety management strategies patients use to mitigate anxiety experienced in the context of eating as determined by diagnostic groups and symptom patterns. Fifty-three eating disorder outpatients were administered the Eating and Anxiety Questionnaire (EAQ) and the Eating Disorder Diagnostic Scale. Ratings indicated significant anxiety in most eating situations, whereas management strategies were more limited yet regularly employed. Factor analysis of the EAQ revealed a 6-factor solution for anxiety management strategies and a 4-factor solution for anxiety-eliciting situations. These results indicate patients with eating disorders report high levels of anxiety associated with eating behaviors but utilize limited yet consistent anxiety management strategies. Effective intervention strategies for managing eating-related anxiety should be incorporated into treatment and may need to be specified for different diagnostic subgroups.


Subject(s)
Anxiety/psychology , Eating/psychology , Feeding and Eating Disorders/psychology , Adolescent , Adult , Aged , Diagnostic Self Evaluation , Feeding and Eating Disorders/diagnosis , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Surveys and Questionnaires
7.
Eat Weight Disord ; 16(3): e177-81, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22290033

ABSTRACT

OBJECTIVE: To examine maintenance of recovery following treatment in an adult anorexia nervosa (AN) population. METHOD: One year follow-up of a randomized clinical trial with 122 participants treated with: cognitive behavioral therapy (CBT), drug therapy (fluoxetine), or a combination (CBT+fluoxetine) for 12 months. Participants were assessed at baseline, end of treatment, and follow-up. The primary outcomes were weight and the global scores from the Eating Disorder Examination (EDE) separately and combined. RESULTS: Fifty-two participants completed the follow-up. Mean weight increased from end of treatment to follow-up. Seventy-five percent (75%) of those weight recovered at end of treatment maintained this recovery at follow-up. Recovery of eating disorder psychopathology was stable from end of treatment to follow-up, with 40% of participants with a global EDE score within normal range. Using the most stringent criteria for recovery, only 21% of the completer sample was recovered. DISCUSSION: The findings suggest that while adults with AN improve with treatment and maintain these improvements during follow-up, the majority is not recovered. Additionally, further research is needed to understand barriers to treatment and assessment completion.


Subject(s)
Anorexia Nervosa/therapy , Cognitive Behavioral Therapy , Fluoxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Anorexia Nervosa/drug therapy , Anorexia Nervosa/psychology , Body Weight , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Personality , Psychiatric Status Rating Scales , Self Concept , Surveys and Questionnaires , Treatment Outcome
8.
Eat Weight Disord ; 16(3): e204-8, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22290037

ABSTRACT

The extent to which cognitive-behavioral therapy (CBT) is helpful in treating individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa is unclear. The purpose of this investigation was to examine the potential efficacy of CBT for eating disorder individuals with bulimic symptoms who do not meet full criteria for bulimia nervosa. Twelve participants with subthreshold bulimia nervosa were treated in a case series with 20 sessions of CBT. Ten of the 12 participants (83.3%) completed treatment. Intent-to-treat abstinent percentages were 75.0% for objectively large episodes of binge eating (OBEs), 33.3% for subjectively large episodes of binge eating (SBEs), and 50% for purging at end of treatment. At one year follow-up, 66.7% were abstinent for OBEs, 41.7% for SBEs, and 50.0% for purging. The majority also reported improvements in associated symptoms. This case series provides support for the use of CBT with individuals with subthreshold bulimia nervosa.


Subject(s)
Bulimia Nervosa/therapy , Bulimia/therapy , Cognitive Behavioral Therapy , Adult , Affect , Bulimia/psychology , Bulimia Nervosa/psychology , Female , Follow-Up Studies , Humans , Severity of Illness Index , Treatment Outcome
9.
Eat Weight Disord ; 15(3): e161-5, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21150251

ABSTRACT

Obesity is a major public health concern in children. Obesity occurs frequently in boys with Duchenne muscular dystrophy (DMD), complicating treatment and impairing functioning. Parent-focused interventions to facilitate weight loss have been successful in other pediatric samples but have not been studied with this population. The current investigation examined the feasibility and potential efficacy of parent-focused treatment to improve healthy eating and physical activity of parents and eating and weight in their sons with DMD. Three families participated in this case series. Resulting changes in body weight among boys with DMD were an outcome variable. Findings indicate inconsistent changes in boys' weight, decreases in parent weight, increases in healthy foods available in the home, and increases in children's perceived quality of life. Participant ratings of treatment suitability and satisfaction were generally favorable. These preliminary findings support the use of parent-focused psychoeducation for the treatment of obesity in children with DMD.


Subject(s)
Feeding Behavior , Muscular Dystrophy, Duchenne/complications , Obesity , Parents , Weight Loss , Adolescent , Adult , Body Weight , Child , Feeding Behavior/psychology , Female , Humans , Male , Obesity/complications , Obesity/physiopathology , Obesity/psychology , Obesity/therapy , Parent-Child Relations , Patient Education as Topic , Surveys and Questionnaires
10.
Eat Weight Disord ; 15(3): e186-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21150253

ABSTRACT

We assessed the relation between season of birth and eating disorder symptoms and personality characteristics in a sample of 880 women with eating disorders and 580 controls from two Price Foundation Studies. Eating disorder symptoms were assessed using the Structured Interview of Anorexic and Bulimic Disorders and the Structured Clinical Interview for DSM-IV. Personality traits were assessed using the Temperament and Character Inventory and the Frost Multidimensional Perfectionism Scale. Date of birth was obtained from a sociodemographic questionnaire. No significant differences were observed 1) in season of birth across eating disorder subtypes and controls; nor 2) for any clinical or personality variables and season of birth. We found no evidence of season of birth variation in eating disorders symptoms or personality traits. Contributing to previous conflicting findings, the present results do not support a season of birth hypothesis for eating disorders.


Subject(s)
Feeding and Eating Disorders , Personality , Adolescent , Adult , Age Factors , Aged , Diagnostic and Statistical Manual of Mental Disorders , Feeding and Eating Disorders/epidemiology , Feeding and Eating Disorders/physiopathology , Feeding and Eating Disorders/psychology , Female , Humans , Middle Aged , Parturition , Seasons , Surveys and Questionnaires , Young Adult
11.
Psychol Sci ; 20(2): 149-54, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19175530

ABSTRACT

We used computer image manipulation to develop a test of perception of subtle gradations in cuteness between infant faces. We found that young women (19-26 years old) were more sensitive to differences in infant cuteness than were men (19-26 and 53-60 years old). Women aged 45 to 51 years performed at the level of the young women, whereas cuteness sensitivity in women aged 53 to 60 years was not different from that of men (19-26 and 53-60 years old). Because average age at menopause is 51 years in Britain, these findings suggest the possible involvement of reproductive hormones in cuteness sensitivity. Therefore, we compared cuteness discrimination in pre- and postmenopausal women matched for age and in women taking and not taking oral contraceptives (progestogen and estrogen). Premenopausal women and young women taking oral contraceptives (which raise hormone levels artificially) were more sensitive to variations of cuteness than their respective comparison groups. We suggest that cuteness sensitivity is modulated by female reproductive hormones.


Subject(s)
Beauty , Contraceptives, Oral, Hormonal , Face , Progesterone/administration & dosage , Adult , Female , Humans , Infant , Middle Aged , Postmenopause , Premenopause , Surveys and Questionnaires , Young Adult
12.
Eur Eat Disord Rev ; 17(6): 426-34, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19760625

ABSTRACT

The aim of the present study was to evaluate the effectiveness of Acceptance and Commitment Therapy (ACT) for treatment of anorexia nervosa (AN) using a case series methodology among participants with a history of prior treatment for AN. Three participants enrolled; all completed the study. All participants had a history of 1-20 years of intensive eating disorder treatment prior to enrollment. Participants were seen for 17-19 twice-weekly sessions of manualized ACT. Symptoms were assessed at baseline, post-treatment and 1-year follow-up. All participants experienced clinically significant improvement on at least some measures; no participants worsened or lost weight even at 1-year follow-up. Simulation modelling analysis (SMA) revealed for some participants an increase in weight gain and a decrease in eating disorder symptoms during the treatment phase as compared to a baseline assessment phase. These data, although preliminary, suggest that ACT could be a promising treatment for subthreshold or clinical cases of AN, even with chronic participants or those with medical complications.


Subject(s)
Adaptation, Psychological , Anorexia Nervosa/psychology , Anorexia Nervosa/therapy , Cognitive Behavioral Therapy/methods , Adult , Awareness , Body Mass Index , Child , Child Abuse, Sexual/psychology , Emotions , Female , Follow-Up Studies , Humans , Middle Aged , Personality Inventory , Pilot Projects , Secondary Prevention , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/psychology , Weight Gain , Young Adult
13.
Behav Res Ther ; 46(7): 887-94, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18501334

ABSTRACT

The current study tested a psychosocial interactive model of perfectionism, self-efficacy, and weight/shape concern within a sample of women with clinically significant bulimic symptoms, examining how different dimensions of perfectionism operated in the model. Individuals with bulimia nervosa (full diagnostic criteria or subthreshold) completed measures of bulimic symptoms, multidimensional perfectionism, self-efficacy, and weight/shape concern. Among those who were actively binge eating (n=180), weight/shape concern was associated with binge eating frequency in the context of high perfectionism (either maladaptive or adaptive) and low self-efficacy. Among those who were actively vomiting (n=169), weight/shape concern was associated with vomiting frequency only in the context of high adaptive perfectionism and low self-efficacy. These findings provide support for the value of this psychosocial interactive model among actively binge eating and purging samples and for the importance of considering different dimensions of perfectionism in research and treatment related to bulimia nervosa.


Subject(s)
Bulimia Nervosa/psychology , Models, Psychological , Vomiting/psychology , Adaptation, Psychological , Adult , Body Image , Diagnostic and Statistical Manual of Mental Disorders , Female , Humans , Self Efficacy
14.
Mycologia ; 99(1): 1-6, 2007.
Article in English | MEDLINE | ID: mdl-17663117

ABSTRACT

Microcycle conidiation and microniche colonization by aspergilli was observed in-situ on various indoor construction and finishing materials. Microcycle conidiation, direct conidiogenesis from a conidium or spore with minimal intervening hyphal development, for several decades has been considered a survival mechanism during stress for a variety of moulds. Adhesive transparent tape mounts and bulk materials from various indoor materials, including air filters from hospitals and healthcare institutions, were transported to the laboratory for light microscopic and scanning electron microscopic observations. Additional materials were held in moist chambers over nonsterile soils and examined periodically for fungal development. Microcycle conidiation was observed usually in areas of sparse fungal development, mostly in association with isolations of members of the Aspergillus flavus-, A. versicolor-, A. niger groups. Branched conidiophores and medusa heads, more often associated with colonization by Eurotium spp., were observed on some preserved woods. These conidiogenesis processes might be factors in the survival and blooms of indoor aspergilli.


Subject(s)
Aspergillus/isolation & purification , Construction Materials/microbiology , Micropore Filters/microbiology , Aspergillus/cytology , Aspergillus/growth & development , Aspergillus/ultrastructure , Hospitals , Microscopy, Electron, Scanning , Spores, Fungal/cytology , Spores, Fungal/ultrastructure
15.
Chronobiol Int ; 33(9): 1267-1279, 2016.
Article in English | MEDLINE | ID: mdl-27494399

ABSTRACT

Despite widely published speculation regarding a potential potency advantage of short-wavelength (blue-appearing) light for Seasonal Affective Disorder (SAD) treatment, there have been few systematic studies. Those comparing short-wavelength to broad-wavelength (white) light under actual clinical conditions suggest equivalent effectiveness. This multicenter, parallel-group design trial was undertaken to compare the effects of light therapy on SAD using blue (~465 nm) versus blue-free (595-612 nm) LED lights. Fifty-six medication-free subjects aged 21-64 years who met DSM-IV-TR criteria for recurrent major depression with winter-type seasonal pattern were enrolled in this blinded study at five participating centers between January and March 2012. Thirty-five subjects met the criteria for randomization to 30 min of either blue (~465 nm) or blue-free (595-612 nm) daily morning light therapy. Twenty-nine subjects completed the study; three subjects withdrew due to treatment-related adverse events, including migraines, and three withdrew for non-study-related reasons. The primary effectiveness variable was depression score (SIGH-ADS) after six weeks of daily light treatment. Secondary effectiveness variables included quality-of-life (QoL) and suicidality ratings. Using an intent-to-treat analysis, mean depression scores were different at baseline for the blue group (29 ± 5 versus 26 ± 5, p = 0.05 blue versus blue-free, respectively), and the initial score was used as a covariate. Baseline scores were not significantly different between treatment groups among those who completed the study, and no significant differences in depression scores were observed after 6 weeks (mean ± SD scores at 6 weeks: 5.6 ± 6.1 versus 4.5 ± 5.3, p = 0.74, blue versus blue-free, respectively). In addition, the proportion of subjects who met remission criteria, defined as a depression score ≤8, was not significantly different between the two groups (p = 0.41); among the 29 subjects who completed the study, 76% of subjects experienced remission by the end of the trial, which coincided with the beginning of spring. The QoL and suicidality ratings were also significantly improved from pre- to post-treatment, with no significant difference between treatments. No subject experienced worsening or non-improved symptoms over the 6-week trial. The main finding of this study is that subjects treated with blue light did not improve more than subjects treated with blue-free light; both showed substantial improvement on multiple measures. Failure to find differences may have resulted from methodological constraints, including a small sample size. Recruitment began mid-winter during an unusually mild season, and the trial was terminated earlier than planned by the study sponsor due to a failure to detect a difference. However, if confirmed in a larger randomized sample, these results suggest that blue wavelengths are not necessary for successful SAD treatment.

16.
Biochim Biophys Acta ; 1489(2-3): 233-48, 1999 Dec 23.
Article in English | MEDLINE | ID: mdl-10673026

ABSTRACT

Incorporation of modified nucleotides into DNA, using the PCR, has allowed us to probe the influence that the exocyclic 5-methyl group of pyrimidines has on DNAse I cleavage and sequence recognition by drugs. The results show that removal of the methyl group from the major groove, made possible by substituting uridine for thymidine, allows DNAse I to cleave more readily at AT-rich regions compared to normal DNA. By contrast, addition of an extra methyl group, contrived by substituting 5-methylcytidine for normal cytidine, allows DNAse I to cleave more readily at GC-rich regions compared to normal DNA. In the cutting pattern of DNA containing both uridine and 5-methyl cytosine, we find the cleavage characteristics of both the single-substituted DNA species combined. Thus, the presence or absence of the exocyclic 5-methyl group in the major groove has a strong influence on the relative intensity of cleavage of phosphodiester bonds by DNAse I. These nucleotide substitutions can also influence the sequence-selective binding of drugs to DNA. Whereas removal of the methyl group (replacement of T with U) generally has little effect on sequence recognition by a variety of drugs, addition of a methyl group (replacement of C with M) generates new binding sites for some intercalators, namely daunomycin, DACA and SN16713.


Subject(s)
Deoxyribonuclease I/metabolism , Pyrimidines/metabolism , Autoradiography , Base Sequence , DNA/metabolism , DNA Footprinting , DNA Primers , Daunorubicin/metabolism , Electrophoresis, Polyacrylamide Gel , Hydrolysis , Molecular Sequence Data , Polymerase Chain Reaction
17.
J Mol Biol ; 291(3): 561-73, 1999 Aug 20.
Article in English | MEDLINE | ID: mdl-10448037

ABSTRACT

The 5-methyl group of thymidine residues protrudes into the major groove of double helical DNA. The structural influence of this exocyclic substituent has been examined using a PCR-made 160 bp fragment in which thymidine residues were replaced with uridine residues. We show that the dT-->dU substitution and the consequent deletion of the methyl group affects the cleavage of DNA by deoxyribonuclease I and micrococcal nuclease. Analysis of the DNase I cleavage sites, in terms of di and trinucleotides, indicates that homopolymeric tracts of d(AT) become significantly more susceptible to DNase I cleavage when uridine is substituted for thymidine residues. The results indicate that removal of the thymidine methyl groups from the major groove at AT tracts induces structural perturbations that transmit into the opposite minor groove, where they can be detected by endonuclease probing. In contrast, DNase I footprinting experiments with different mono and bis-intercalating drugs reveal that dT-->dU substitution does not markedly affect sequence-specific drug-DNA recognition in the minor or major groove of the double helix. The consequences of demethylation of thymidine residues are discussed in terms of changes in the minor groove width connected to variations in the flexibility of DNA and the intrinsic curvature associated with AT tracts. The study identifies the methyl group of thymine as an important molecular determinant controlling the width of the minor groove and/or the flexibility of the DNA.


Subject(s)
DNA, Bacterial/chemistry , DNA, Bacterial/metabolism , Endonucleases/metabolism , Thymine/chemistry , Thymine/metabolism , Base Sequence , Binding Sites/genetics , DNA Primers/genetics , DNA, Bacterial/genetics , Deoxyribonuclease I/metabolism , Intercalating Agents , Methylation , Micrococcal Nuclease/metabolism , Molecular Sequence Data , Uridine/chemistry , Uridine/metabolism
18.
Arch Gen Psychiatry ; 56(1): 63-9, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9892257

ABSTRACT

BACKGROUND: Since bulimia nervosa's introduction to the psychiatric nomenclature in 1979, data concerning long-term outcome have been largely unavailable. METHODS: Women with the diagnosis of bulimia nervosa between 1981 and 1987 who participated in 1 of 2 studies were located and invited to participate in follow-up assessments. RESULTS: More than 80% of the women from these studies participated in follow-up assessments and the results represent findings for 173 women. More than 10 years following presentation (mean+/-SD length of follow-up, 11.5+/-1.9 years), 11% of this sample met full criteria for bulimia nervosa, and 0.6% met full criteria for anorexia nervosa. An additional 18.5% met criteria for eating disorder not otherwise specified, and 69.90% of this sample were either in full or in partial remission. For predictive factors, only the duration of the disorder at presentation and history of substance use problems demonstrated prognostic significance. Baseline treatment condition was not associated with remission of disordered eating symptoms by the follow-up assessment. CONCLUSIONS: The findings suggest that the number of women who continue to meet full criteria for bulimia nervosa declines as the duration of follow-up increases; approximately 30%, however, continued to engage in recurrent binge eating or purging behaviors (incidence rate, 0.026 cases per person-years). A history of substance use problems and a longer duration of the disorder at presentation predicted worse outcome.


Subject(s)
Bulimia/therapy , Adult , Age of Onset , Body Image , Body Weight , Bulimia/epidemiology , Bulimia/psychology , Comorbidity , Female , Follow-Up Studies , Humans , Incidence , Longitudinal Studies , Mental Disorders/epidemiology , Prognosis , Psychiatric Status Rating Scales , Psychotherapy , Psychotropic Drugs/therapeutic use , Risk Factors , Severity of Illness Index , Substance-Related Disorders/epidemiology , Surveys and Questionnaires , Treatment Outcome
19.
Am J Psychiatry ; 157(1): 136-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10618030

ABSTRACT

OBJECTIVE: The authors sought to investigate the predictive validity of bulimia nervosa as a diagnostic category. METHOD: More than 10 years after they appeared as patients with bulimia nervosa, 177 women (participation rate=79.7%) completed follow-up assessments. RESULTS: Among the women with a current eating pathology, most engaged in recurrent binge eating and purging. Anorexia nervosa and binge eating disorder were relatively uncommon. Eating disorder outcome was significantly related to the presence of mood, substance use, and impulse control disorders but not to the presence of anxiety disorders. CONCLUSIONS: These results support the validity of bulimia nervosa as a diagnostic category that is distinct from anorexia nervosa. Furthermore, these results suggest that bulimic symptoms are associated with disorders involving distress and disinhibition.


Subject(s)
Bulimia/diagnosis , Anorexia Nervosa/diagnosis , Anorexia Nervosa/epidemiology , Anorexia Nervosa/psychology , Bulimia/epidemiology , Bulimia/psychology , Comorbidity , Diagnosis, Differential , Disruptive, Impulse Control, and Conduct Disorders/epidemiology , Female , Follow-Up Studies , Humans , Mood Disorders/epidemiology , Outcome Assessment, Health Care , Predictive Value of Tests , Prognosis , Psychiatric Status Rating Scales/statistics & numerical data , Reproducibility of Results , Substance-Related Disorders/epidemiology
20.
Am J Psychiatry ; 157(8): 1302-8, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10910795

ABSTRACT

OBJECTIVE: The aim of this study was to discover clinically useful predictors of attrition and outcome in the treatment of bulimia nervosa with cognitive behavior therapy. METHOD: Pretreatment, course of treatment, and outcome data were gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were treated with 18 sessions of manual-based cognitive behavior therapy in a three-site study. Differences between dropouts and nondropouts and between recovered and nonrecovered participants were first examined descriptively, and signal detection analyses were then used to determine clinically significant cutoff points predicting attrition and abstinence. RESULTS: The dropouts were characterized by more severe bulimic cognitions and greater impulsivity, but it was not possible to identify clinically useful predictors. The participants with treatment failures were characterized by poor social adjustment and a lower body mass index, presumably indicating greater dietary restriction. However, early progress in therapy best predicted outcome. Signal detection analyses revealed that poor outcome was predicted by a reduction in purging of less than 70% by treatment session 6, allowing identification of a substantial proportion of prospective failures. CONCLUSIONS: A cutoff point based on reduction of purging by session 6 usefully differentiates patients who will and will not respond to cognitive behavior therapy for bulimia nervosa, potentially allowing early use of a second therapy.


Subject(s)
Bulimia/therapy , Cognitive Behavioral Therapy , Adult , Bulimia/psychology , Educational Status , Female , Humans , Patient Dropouts , Patient Selection , Probability , Regression Analysis , Treatment Outcome
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