Search

Both clinical and empirical studies suggest that insecure attachment is common in eating disordered populations. Clinical studies have addressed mother-daughter interactions, but there has been little empirical research into the mother's own attachment patterns and whether there might be intergenerational transmission of these patterns. We aimed to examine the attachment status of patients with severe anorexia nervosa and their mothers, using the 'gold standard' Adult Attachment Interview (AAI). We predicted: (1) a high level of insecurity among the patients (women with anorexia nervosa with or without bulimic behaviours); (2) that the mothers would show a higher rate of insecurity than predicted by population norms; and (3) that there might be attachment style associations within mother-daughter pairs. Twenty consecutive in-patients with a DSM-IV diagnosis of anorexia nervosa were interviewed using the AAI, as were 12 of their mothers. The mental state of daughters was rated by experienced clinicians, and that of mothers by the Clinical Interview Schedule (Revised). AAIs were transcribed and rated by expert raters. Nineteen (95%) daughters and 10 (83%) mothers were rated insecure on the AAI. Of these, 15 (79%) daughters and seven (70%) mothers were dismissive in type. We did not find an association between mothers' and daughters' attachment style. The incidence of unresolved loss was high among the mothers (67%). Idealization scores were high and reflective functioning scores low in both mother and daughter groups. Women with anorexia nervosa and their mothers commonly have a dismissive attachment style. Low levels of reflective functioning and high idealization scores are found in both groups, and may be learned (or transmitted) from mother to daughter. A difficulty in emotional processing, exemplified by unresolved loss, may be transmitted to daughters, and act as a risk factor for the development of anorexia nervosa.

The deposition of abnormal protein fibrils is a prominent pathological feature of many different 'protein conformational' diseases, including some important neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), motor neurone disease and the 'prion' dementias. Some of the fibril-forming proteins or peptides associated with these diseases have been shown to be toxic to cells in culture. A clear understanding of the molecular mechanisms responsible for this toxicity should shed light on the probable link between protein deposition and cell loss in these diseases. In the case of the beta-amyloid (Abeta), which accumulates in the brain in AD, there is good evidence that the toxic mechanism involves the production of reactive oxygen species (ROS). By means of an electron spin resonance (ESR) spin-trapping method, we have shown recently that solutions of Abeta liberate readily detectable amounts of hydroxyl radicals upon incubation in vitro followed by the addition of small amounts of Fe(II). We have also obtained similar results with alpha-synuclein, which accumulates in Lewy bodies in PD. Our data suggest that hydrogen peroxide accumulates during Abeta or alpha-synuclein incubation and that this is subsequently converted to hydroxyl radicals, on addition of Fe (II), by Fenton's reaction. Consequently, we now support the idea that one of the fundamental molecular mechanisms underlying the pathogenesis of cell death in AD, PD, and possibly some other protein conformational diseases, could be the direct production of ROS during formation of the abnormal protein aggregates. This hypothesis suggests a novel approach to the therapy of this group of diseases.

Background: There is controversy as to whether PTSD can develop following a brain injury with a loss of consciousness. However, no studies have specifically examined the influence of the memories that the individuals may or may not have on the development of symptoms., Aims: To consider how amnesia for the traumatic event effects the development and profile of traumatic stress symptoms., Method: Fifteen hundred case records from an Accident and Emergency Unit were screened to identify 371 individuals with traumatic brain injury who were sent questionnaires by post. The 53 subsequent valid responses yielded three groups: those with no memory (n = 14), untraumatic memories (n = 13) and traumatic memories (n = 26) of the index event. The IES-R was used as a screening measure followed by a structured interview (CAPS-DX) to determine caseness and provide details of symptom profile., Results: Groups with no memories or traumatic memories of the index event reported higher levels of psychological distress than the group with untraumatic memories. Ratings of PTSD symptoms were less severe in the no memory groups compared to those with traumatic memories., Conclusions: Psychological distress was associated with having traumatic or no memories of an index event. Amnesia for the event did not protect against PTSD; however, it does appear to protect against the severity and presence of specific intrusive symptoms.

The direct formation of free radicals from Abeta has been suggested to be a key neurotoxic mechanism in Alzheimer's disease (AD). We have explored the possibility of the spontaneous formation of peptide-derived free radicals during the incubation of Abeta 1-40 by ESR spectroscopy using N-tert-butyl-alpha-phenylnitrone (PBN), 5,5-dimethyl-1-pyrroline N-oxide (DMPO), alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN), and 3,5-dibromo-4-nitrosobenzenesulfonic acid sodium salt (DBNBS) as spin traps. Employing PBN, we observed spectra during the incubation of beta-amyloid peptide, at 37 degrees C, which included adducts of 2-methyl-2-nitrosopropane (MNP), despite rigorous purification of the PBN before incubation. The formation of some of these adducts was found to be enhanced by ambient laboratory light. Our experiments have led us to propose a hypothesis that PBN undergoes hydrolysis and decomposition in the presence of oxidants, which explains the origin of all of the PBN and MNP adducts observed (even when the PBN is highly purified). Hydrogen peroxide, formed during incubation, could play a major role as an oxidant in these experiments. Of the other three spin traps, only DMPO gave (very weak) spectra, but these could be assigned to its hydroxyl radical adduct, formed as an artifact by the nucleophilic addition of water to DMPO, catalyzed by trace levels of iron ions. Thus, while spectra are observed during our experiments, none of them can be assigned to adducts of radicals derived from the peptide and, therefore, our data do not support the suggestion that radicals are spontaneously formed from beta-amyloid peptide.

Some rare inherited forms of Parkinson's disease (PD) are due to mutations in the gene encoding a 140-amino acid presynaptic protein called alpha-synuclein. In PD, and some other related disorders such as dementia with Lewy bodies, alpha-synuclein accumulates in the brain in the form of fibrillar aggregates, which are found inside the neuronal cytoplasmic inclusions known as Lewy bodies. By means of an electron spin resonance (ESR) spin trapping method, we show here that solutions of full-length alpha-synuclein, and a synthetic peptide fragment of alpha-synuclein corresponding to residues 61-95 (the so-called non-Abeta component or NAC), both liberate hydroxyl radicals upon incubation in vitro followed by the addition of Fe(II). We did not observe this property for the related beta- and gamma-synucleins, which are not found in Lewy bodies, and are not linked genetically to any neurodegenerative disorder. There is abundant evidence for the involvement of free radicals and oxidative stress in the pathogenesis of nigral damage in PD. Our new data suggest that the fundamental molecular mechanism underlying this pathological process could be the production of hydrogen peroxide by alpha-synuclein.

The cmc and IC50 values of the beta-amyloid (Abeta) aggregation inhibitors, 3-p-toluoyl-2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 1, and 2-[4'-(3-diethylaminopropoxy)-phenyl]-benzofuran 2 have been determined. After comparison of the cmc data and biological data (IC50 values), we conclude that these active benzofurans do not act as surfactants or micelles at the concentration required to inhibit beta-amyloid-peptide aggregation.

Objective: There is a wide literature suggesting abnormal mother-daughter and familial attachment patterns in individuals with eating disorders. We surmised that this insecurity would extend to adult attachment relationships., Methods: The Reciprocal Attachment Questionnaire (RAQ) was administered to all inpatients and outpatients at a tertiary referral eating disorders unit over a given period of time, and to controls. The RAQ operationalizes the key components of reciprocal attachment, and is in close theoretical agreement with the Adult Attachment Interview., Results: Patients scored significantly higher than controls on most scales of the RAQ, most notably on Compulsive Care-Seeking and Compulsive Self-Reliance. We did not find any associations between eating disorder diagnoses and particular attachment profiles., Conclusions: A basic "pull-push" dilemma was demonstrated in the reciprocal attachment relationships of eating-disordered subjects. This dilemma bedevils attempts at therapy and may illuminate the strong feelings elicited by these patients in their therapists. The association of attachment style with particular disorder subgroup diagnoses is complicated. Childhood attachment insecurity may provide a vulnerability whose symptomatic manifestation is colored by later events., (Copyright 2000 by John Wiley & Sons, Inc.)

Objective: This study examined pretreatment variables to predict outcome in two treatments for bulimia nervosa., Method: Patients were offered either 16 weeks of cognitive-behavioral therapy (CBT) or a self-treatment manual followed by up to 8 weeks of CBT (sequential group). Using complete data, stepwise regression analyses were performed., Results: It was found that a longer duration of illness and lower binge frequency predicted a better outcome both at the end of treatment (p < .001) and at 18 months of follow-up (p < .005). In the sequential group, lower pretreatment binge frequency predicted better outcome at the end of treatment (p < .05) and at 18 months of follow-up (p < .05). In the CBT group, longer duration of illness predicted better outcome at the end of treatment (p < .02)., Discussion: It is concluded that (1) those with more frequent binging may require a more intense intervention and (2) those who have been ill longer may be more motivated to respond to treatment.

Background: An epidemiological study of anorexia nervosa and bulimia nervosa in primary care was performed using the General Practice Research Database (GPRD)., Method: The GPRD was screened between 1988 and 1994 for newly diagnosed cases of anorexia nervosa and bulimia nervosa. The validity of the computer diagnosis was established by obtaining clinical details from a random sample of the general practitioners (GPs)., Results: Incidence rates for detection of cases by GPs in 1993 was 4.2 per 100,000 population for anorexia nervosa, and 12.2 per 100,000 for bulimia nervosa. The relative risks of females to males was 40:1 for anorexia nervosa and 47:1 for bulimia nervosa. A threefold increase in the recording of bulimia nervosa was found from 1988 to 1993. Eighty per cent of anorexia nervosa cases and 60% of bulimia nervosa cases were referred to secondary care., Conclusion: There is a continuing expansion of service need for bulimia nervosa. The majority of cases of eating disorders are referred to secondary services. There is scope for more effective management of bulimia nervosa in primary care.

Background: The aim of this study was to evaluate the effectiveness of a stepped care approach to the treatment of bulimia nervosa: a self-care manual followed, if necessary, by a course of attenuated cognitive behavioural treatment (CBT) in comparison with standard CBT., Method: One hundred and ten patients, presenting at a tertiary referral centre with ICD-10 bulimia nervosa or atypical bulimia nervosa, were randomly assigned to one of two treatment conditions; a) a sequential treatment group: 8 weeks with a self-care manual followed by up to eight sessions of CBT (if still symptomatic) or b) 16 sessions of CBT., Results: Bulimic symptoms improved significantly in both groups with no significant differences between the two groups on any of the measures at the end of treatment or at 18 months follow-up. At end of treatment 30% (95% CI: 18-46%) of the sequential group and 30% (95% CI: 17-47%) of the standard treatment group were free from all bulimic symptoms. Sixteen of those in the sequential group improved significantly with self-care and did not require additional treatment. The median number of sessions taken by the sequential group was three (95% CI: 0-6). At 18 months follow-up 40% (95% CI: 23-59%) of the sequential group and 41% (95% CI: 25-59%) of the CBT group were symptom free., Conclusions: A sequential approach to the treatment of bulimia may be as effective as standard CBT and can considerably reduce the amount of therapist contact required.

The effects of signal onset/offset envelope on the underwater hearing thresholds of a harbor seal (Phoca vitulina) were measured. Pure-tone, 540-ms pulses at 2, 4, 8, and 16 kHz were presented as test signals. An ANOVA revealed that there were no significant differences between repeated threshold measures for abrupt onset/offset signal envelopes versus slow onset/offset signal envelopes [F = 4.380, d.f. = (1,18), p > 0.05]. Seal vocalizations which have an abrupt onset/offset may be serving a short-range communicative function by helping the listener determine the direction of a nearby sender.

Many seal vocalizations consist of frequency swept tones. The signal detection thresholds of a harbor seal (Phoca vitulina) and of human listeners were measured using ascending and descending frequency swept tones at 1/3- and 1-oct bandwidths. The swept tones increased or decreased exponentially and traversed the same frequency range. The sweeps were centered on 2, 4, and 8 kHz for the seal study and 0.5, 1, and 2 kHz for the human listeners. The bandwidth of the sweep did not affect signal detection abilities of either the seal or human listeners. The seal had lower signal detection thresholds (1-5 dB) when presented with the descending frequency swept tones (F = 32.04, df = (1,31), p < 0.000001). Human listeners also had lower detection thresholds for descending frequency swept tones (t = -4.78, df = 52, p < 0.0001). Pinniped ascending frequency swept calls may not function as well as descending frequency sweeps for long-distance communicative signals.

Rat monoclonal anti-idiotype antibodies (mAb2) were raised against two mouse monoclonal antibodies (mAb1), 1D10 and 2A6, with specificity for the M-like protein of Streptococcus equi. The capacity of the mAb2 to inhibit the binding between the corresponding mouse mAb1 against which the mAb2 were raised and the M-like protein was investigated in an inhibition EIA. One of the ten mAb2 examined, namely 5D1 (anti-mAb1 1D10), was able to inhibit this binding. The mAb2 5D1 bound to the mAb1 1D10 in such a way as to completely inhibit the subsequent binding of the M-like protein antigen to the paratope of the mAb1 1D10. The mAb2 5D1 is likely to represent a true image of the M-like protein antigen and may thus be described as an Ab2 beta anti-idiotype antibody.

Anti-idiotype antibodies that carry an internal image of an antigen epitope (Ab2 beta antibodies) can be used in vaccine preparations to favourably manipulate the immune network. These vaccines have been shown to induce protective immunity in animals that have not been intentionally exposed to the native antigen epitope. This review attempts to define certain theoretical and practical aspects of immunological network manipulations and their relevance to Ab2 beta internal image anti-idiotype antibody vaccine design.

We have developed an in vivo passive transfer assay using mice to identify monoclonal antibodies (mAbs) which offer protection against Streptococcus equi infection. The assay was developed using serum antibodies collected from horses convalescing from strangles. In this study, we show that a preparation of M-like protein, acid-extracted from S. equi, affords 80% protection to mice immunized with it. A number of mouse mAbs directed against a preparation of M-like protein were then assessed for their ability to passively protect mice against challenge with a lethal dose of the bacteria. Two mAbs, 1D10 and 2A6, were shown to be highly protective. It was also demonstrated, by means of a competitive enzyme immunoassay, that these mAbs recognized different epitopes in the preparation. Examination of a dose-response curve for mAbs 1D10 and 2A6 revealed that optimal levels of protection were achieved using 1 mg of either 1D10 or 2A6, or 0.5 mg 1D10 and 0.5 mg 2A6 given together. Immunological reactivity of these mAbs with a preparation of M-like protein showed that the antigens they recognized were comparable in size to some of the antigens recognized by convalescent horse serum antibodies. The role of immunoglobulin isotype in conferring protection is discussed.

(R)-4-(N,N-Dimethylammonio)-3-hydroxybutanoate [(R)-norcarnitine] monohydrate, C6H13NO3.H2O, Mr = 165.2, triclinic, P1, a = 5.9081 (5), b = 6.0438 (4), c = 6.9084 (7) A, alpha = 65.584 (6), beta = 81.957 (8), gamma = 77.771 (6) degrees, V = 219.1 (1) A3, Z = 1, Dx = 1.252 g cm-3, lambda(Cu K alpha) = 1.54184 A, mu = 8.46 cm-1, F(000) = 90, T = 296 K, R = 0.035 for 1763 observations (of 1772 unique data). Intermolecular hydrogen bonding dominates the structure. The molecule of water contacts three different zwitterions, with O...O distances 2.7767 (13), 2.720 (2) and 2.722 (2) A. A hydrogen bond between carboxylate and dimethylammonio links the zwitterions in head-to-tail motif, N...O 2.672 (2) A. Comparison with two other 4-ammonio-3-hydroxybutanoates reveals that the title compound adopts a different conformation along the backbone, N(+)--C--C(OH)--C--CO2-, with N(+)--C--C(OH)--C anti and C--C(OH)--C--CO2- gauche-.

Mouse monoclonal (Ab1) anti-tetanus toxin/toxoid antibodies were used to raise Ab2 beta (tetanus toxin/toxoid internal image bearing) anti-idiotype antibodies in rabbits. Those rabbit serum antibodies (Ab2 beta) that did not bind to mouse serum proteins on an affinity column gave rise to an Ab3 anti-tetanus toxin/toxoid antibody response in mice. Rabbit serum antibodies that did bind to the affinity column, when eluted and used to inoculate mice also gave rise to an Ab3 anti-tetanus toxin/toxoid antibody response. It is suggested that one population of rabbit Ab2 beta anti-idiotype antibodies (unbound fraction) bears a partial or complete internal image of a tetanus epitope (Ab2 beta 1) while others (bound fraction) bear a complete or partial mirror image of a mouse immunoglobulin epitope as well (Ab2 beta 2).

Primary immune responses to tetanus toxoid (TT) and primary and secondary immune responses to a rabbit TT internal image bearing anti-idiotype antibody (Ab2 beta 1) inoculated in Freund's complete adjuvant (FCA), saline (SAL) or syntex adjuvant formulation vehicle (SAF) via the intraperitoneal or subcutaneous route, were examined in mice. High anti-TT antibody (Ab3) titres are reported although the titre and persistence of the antibody response varied according to the adjuvant used in the priming and challenge inocula of Ab2 beta 1. Mouse Ab3 antibodies were elicited in mice inoculated with rabbit Ab2 beta 1 antibodies which in turn were elicited by an inoculum of mouse monoclonal anti-TT Ab1 antibody. Ab3 was shown to be identical to Ab1 by immunoblot analysis. Primary and secondary immune responses elicited by rabbit Ab2 beta 1 antibody protected mice against a lethal dose of tetanus toxin.

Normal infants have been shown to respond to a relatively low concentration of inhaled histamine. However, those studies used partial maximal expiratory flow volume (PMEFV) curves to assess lung function. In order to directly compare responsiveness between infants and older children, we compared bronchial responsiveness to histamine between a group of 45 normal infants, median age 4 wk (range 2 to 6 wk) and a group of 30 nonasthmatic older children, median age 10 yr (range 5 to 15 yr) using PMEFV curves in both groups to assess lung function. In the infant group, PMEFV curves were generated using the forced expiratory flow volume technique. For the older children, PMEFV curves were generated by voluntary effort. The provocative concentration of histamine that produced a 40% fall (PC40) in maximum flow at functional residual capacity (VmaxFRC) was calculated from the PMEFV curves. The geometric mean PC40 of the infants (1.02 g/L) was lower than the geometric mean of the older children (3.4 g/L) (p less than 0.001). However, these results were then corrected for dilution of the aerosol due to air entrainment (AE). Corrected values of PC40 were not significantly different between infants and older children. These results demonstrate the importance of accounting for AE in the evaluation of histamine responsiveness and suggest that bronchial responsiveness may be similar in normal infants and older children.

A procedure by which crystalline sodium norcarnitine can be prepared in large quantities and high yields has been developed. Carnitine is selectively demethylated by thiophenoxide ion in N,N-dimethylethanolamine. The reactive thiophenoxide ion is generated in situ by addition of thiophenol to this basic reaction solvent. Hence, sodium thiophenoxide, which has been used in similar applications, but is difficult to prepare, can be avoided. Accordingly, reaction of (R,S)-carnitine followed by aqueous azeotropic distillation of byproducts as well as excess starting materials and then by neutralization with sodium hydroxide gave sodium norcarnitine in 89% yield. (R)-Carnitine gave 91% yield of (R)-norcarnitine zwitterion before neutralization. A method for the facile preparation of radiolabeled (R)-carnitine is also described. Thus, methylation of sodium norcarnitine with methyl iodide in methanolic acetone produced carnitine, which precipitated, and sodium iodide, which was soluble.

Threshold changes associated with separating a signal source and a masking white noise source from 0 degree to 90 degrees were determined for 0.5, 1 and 8 kHz pure tones and click trains. No changes occurred for the 0.5 and 1 kHz pure tones. Masked thresholds of 8 kHz pure tones and click trains decreased linearly by 9 and 13 dB respectively as angular separation was moved from 0 degree to 90 degrees. Changes in click train stimuli masked thresholds did not change significantly when the ear directed toward the masking source was occluded (11 dB drop at 90 degrees). The absence of changes at low frequencies and the similarity in magnitude of the changes in signals containing high frequency components with the responses to the monaural click trains, suggests that the threshold changes can be attributed to a head shadow effect. The casting of a sound shadow effectively lowers the noise level on the shielded side. These findings question the importance of cross-correlation techniques when detecting signals in noise.

Advanced age is not, per se, an indication for a different treatment approach, although certain modifications in the treatment plan are required. Recognition and management of anxiety disorders in the elderly must be prompt to interrupt the vicious cycle of anxiety-depression, physical illness, and other stresses.