A randomized controlled comparison of integrative cognitive-affective therapy (ICAT) and enhanced cognitive-behavioral therapy (CBT-E) for bulimia nervosa.

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.

Moving towards the immunodiagnosis of staphylococcal intramammary infections.

Bovine mastitis is the primary disease of dairy cattle that has a great impact on the dairy industry. It is estimated that worldwide economic losses due to mastitis range between US$82 and US$131 per cow/year. A fast and efficient diagnosis of the disease remains a major bottleneck that directly influences the speed with which treatment decisions and management are undertaken. Microbiological culture remains the gold standard in the identification of bacteria that cause mastitis, but the method has inherent limitations, such as a delay in obtaining results and cost, and requires special care during the collection and processing of the sample. For this reason, multiple groups have devoted efforts to develop alternative methods that, preferably, can be easily accomplished in the field. The specificity of the antigen-antibody reaction has enabled the emergence of major diagnostic methods used in clinical practice, such as immunoassays, which have significant advantages in terms of speed, sensitivity, specificity, and portability. Commercially, immunodiagnostics have been used in the detection of various diseases in cattle. However, in several cases, only a presumptive diagnosis can be made, which requires confirmation using culture-based methods. This review discusses the immunological-based assays developed since the 1990s for the detection of Staphylococcus aureus, which is considered the primary pathogen of contagious bovine mastitis. Although no ideal antigens ensure the accurate performance of tests and the costs need to be reduced to allow for good market competitiveness, immunoassays, particularly lateral flow immunoassay and immunoagglutination, have emerged as promising tests to be used in the field.

Immunorelevant proteins for the diagnosis of bovine staphylococcal mastitis.

Staphylococcus aureus is a leading cause of bovine mastitis, a condition in which the udder of the cow is inflamed, reducing the quality and quantity of milk produced. Staphylococcal mastitis is a common infection that can develop into a chronic form. The segregation of infected animals is an important preventive practice but relies on an effective diagnostic method. For this purpose, we constructed a genomic library of S. aureus, and a screening step was conducted with antiserum produced using the total protein extract of the pathogen. The nucleotide sequences of the immunoselected clones were aligned with the genome of bovine S. aureus RF122, which enabled the identification of 65 different loci, including proteins related to metabolism, adhesion and cell wall production, toxins, regulatory proteins, and hypothetical proteins. The subcellular location of the immunoreactive polypeptides was also determined. Fifty-two percent were cytoplasmic, 34 % were located in areas exposed to the host's immune system, and for 14 %, the location could not be determined. In silico analysis of the presence of these proteins in mastitis pathogens showed that Fib, ClfA, and the hypothetical protein SAB0166 were the only proteins specific for S. aureus. Therefore, these proteins are promising candidates for the serodiagnosis of staphylococcal mastitis.

Examining a psychosocial interactive model of binge eating and vomiting in women with bulimia nervosa and subthreshold bulimia nervosa.

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.

The crystal structure of pertussis toxin.

BACKGROUND: Pertussis toxin is an exotoxin of the A-B class produced by Bordetella pertussis. The holotoxin comprises 952 residues forming six subunits (five different sequences, S1-S5). It plays an important role in the development of protective immunity to whooping cough, and is an essential component of new acellular vaccines. It is also widely used as a biochemical tool to ADP-ribosylate GTP-binding proteins in the study of signal transduction. RESULTS: The crystal structure of pertussis toxin has been determined at 2.9 A resolution. The catalytic A-subunit (S1) shares structural homology with other ADP-ribosylating bacterial toxins, although differences in the carboxy-terminal portion explain its unique activation mechanism. Despite its heterogeneous subunit composition, the structure of the cell-binding B-oligomer (S2, S3, two copies of S4, and S5) resembles the symmetrical B-pentamers of the cholera toxin and Shiga toxin families, but it interacts differently with the A-subunit. The structural similarity is all the more surprising given that there is almost no sequence homology between B-subunits of the different toxins. Two peripheral domains that are unique to the pertussis toxin B-oligomer show unexpected structural homology with a calcium-dependent eukaryotic lectin, and reveal possible receptor-binding sites. CONCLUSION: The structure provides insight into the pathogenic mechanisms of pertussis toxin and the evolution of bacterial toxins. Knowledge of the tertiary structure of the active site forms a rational basis for elimination of catalytic activity in recombinant molecules for vaccine use.

Computers and psychiatry. Promises to keep.

The potential of computer-based psychiatric information systems is still largely undeveloped. Conceptual, technical, cost, and procedural problems have limited the impact of computers, but there are programs that have been successful or that show promise. While changes in the philosophy of psychiatric computer applications are on-going, a cost-effective, widely available clinical computer system has been developed.

Psychiatric disorders in patients with spinal cord injuries.

Although previous studies have reported that all patients with spinal cord injuries experience depression, they have not distinguished between despondency and depressive disorder. Of 30 patients with spinal cord lesions and depressive disorders diagnosed using the Schedule for Affective Disorders and Schizophrenia and the Research Diagnostic Criteria (RDC). 15 patients had RDC diagnoses before or after their injury. A depressive disorder developed in nine after injury. Eight depressive disorders developed within a month of the injury. Postinjury depressive disorders were more common in patients with complete spinal cord lesions but were divided equally between paraplegics and quadriplegics. Only one patient received antidepressants. The remainder recovered without treatment other than the rehabilitation program. The accident causing the injury seemed related to a psychiatric disorder before injury in six patients (four alcoholics and two hypomanics) and to drinking before the accident in 15 patients.

Intravenous streptokinase for thrombolysis of occluded arteriovenous access. Its use in patients undergoing hemodialysis.

Thrombosis of arteriovenous access is a major cause of morbidity in the patient population undergoing hemodialysis. This investigation utilized the technique of infusing streptokinase directly into the afferent limb of an occluded graft or fistula to restore patency. A total of seven patients was studied, one patient on two separate occasions nine months apart. Total clot lysis was observed in five of eight infusions. Partial clot lysis was seen in two of eight infusions, although one of these patients required thrombectomy to ensure persistent functioning of the fistula. One of the eight episodes was unsuccessful. A postinfusion fistulogram was performed on seven of eight occasions and demonstrated partial clot lysis in two patients or a stenotic lesion requiring surgical revision in two other cases. In conclusion, streptokinase infusion into the thrombosed vascular access appears to be a safe and efficacious technique for this patient population.

The role of the VL- and VH-segments in the preferential reassociation of immunoglobulin subunits.

Competitive reassociation experiments, in which equimolar amounts of two different L-chains were allowed to compete for a limiting amount of H-chain, were performed to assess the role of the V kappa- and J kappa-segments on the ability of an L-chain to compete. Using H- and L-chains from the murine anti-phosphorylcholine (PC) myelomas, TEPC15, MOPC167 and MCPC603, and a series of V kappa 21 L-chains, it was found that the V kappa 21 L-chains competed uniformly better than the anti-PC L-chains, when the anti-PC H-chains were used, despite any differences in the J-segments of the competing L-chains. In addition, when the anti-PC L-chains, which all employ identical J kappa-segments but very diverse V kappa-segments, were in competition against each other, a hierarchy of competitive ability existed which was independent of whether the chains were autologous or heterologous and independent of antigen binding activity. Competitive reassociation experiments between the V kappa 21 and anti-PC L-chains were also performed using the heterologous anti-lysozyme monoclonal HyHEL-10 H-chain or the anti-galactan J539 H-chain, and it was found that the relative competitive ability of the V kappa 21 L-chains with respect to the anti-PC L-chains was dependent on which H-chain was employed. The results suggested that the main factor favouring preferential reassociation by any particular L-chain was the V kappa-segment and that the effects of the J kappa-segment could not be observed where a high degree of diversity in the V-segments existed. Furthermore, while the results implied that specific pairs of VH- and VL-domains had a higher affinity for each other, this was not a necessary criterion in the formation of autologous pairs of H- and L-chains as demonstrated by the preferential heterologous reassociation of the V kappa 21 L-chains over the autologous anti-PC L-chains. These results were consistent with the independent, random rearrangement of immunoglobulin H- and L-chain V-domain gene segments and predict that the hypothetical repertoire of antibodies is not limited by the selection of specific pairs of high-affinity VH-VL domains.

Strategy for developing a genetically-engineered whole-virus vaccine against HIV.

The production of genetically-engineered, noninfectious virions of human immunodeficiency virus (HIV) represents a novel approach to the development of a safe and effective vaccine for the acquired immune deficiency syndromes (AIDS). Insofar as preparations of inactivated simian immunodeficiency virus (SIV) are now demonstrating protection in immunization-challenge studies in rhesus monkeys, a safe preparation of noninfectious HIV virions produced in a genetically-engineered cell line becomes a logical candidate vaccine for studies in humans. These particles, or pseudovirions, offer distinct advantages over the use of inactivated HIV for human AIDS vaccines. Guarantees of safety without the requirement for inactivation and their potential for structural modification for the modulation of immunogenicity are compelling reasons for the acceptance of HIV pseudovirions as a candidate vaccine in humans.

Contribution of the VK4 light chain to antibody specificity for lysozyme and beta (1,6)D-galactan.

The VL amino acid sequence of an anti-lysozyme hybridoma protein, HyHEL-5, was determined. HyHEL-5 expresses a V region of the VK4 family and JK1. The VK4 family also includes light chains from galactan binding antibodies, although sequence comparisons suggest that a different member of this family is used to encode HyHEL-5. The HyHEL-5 light chain has a deletion of residue 96, such that L3 is one residue shorter than the majority of murine L3. Chain recombination experiments, employing H and L chains from different anti-galactan and anti-lysozyme binding antibodies, were performed to examine the contribution of the H and L chain in dictating specificity for either galactan or the lysozyme epitope recognized by HyHEL-5. The results indicate that, although the ability to bind galactan vs lysozyme is absolutely heavy-chain dependent, having the appropriate heavy chain is not sufficient for specific high affinity binding. Both the L chains from HyHEL-5 and J539 (a galactan-binding myeloma protein) were capable of supporting binding to galactan in combination with the J539 H chain, but affinity for galactan is less with the HyHEL-5 L chain. Only VK4 L chains supported binding of the HyHEL-5 heavy chain to the HyHEL-5 epitope, although binding with the J539 L chain was low affinity and relatively nonspecific.

Structural basis for the preferential association of autologous immunoglobulin subunits: role of the J region of the light chain.

We have used a series of sequenced V kappa 21 L-chains produced from murine myelomas to determine whether the V or J segment of the V region is responsible for dictating preferential recombination. In each competitive recombination, equimolar amounts of two different L-chains, selected on the basis of common V or J segments, were allowed to compete for a limiting amount of H-chain. It was found that the J segment of the L-chain was primarily responsible for dictating the ability of a chain to compete and that the nature of residue 96, the first residue of the J segment, was particularly important. Specifically, charged residues caused the L-chain to compete poorly against L-chains with hydrophobic side chains at this position. Furthermore, if Phe or, to a lesser extent, Tyr were present at position 96, the L-chain competed more successfully than chains with Trp-96 or Leu-96. This suggests that both the aromaticity and size of this residue were important factors in determining preferential recombination. It was also found that all other residues in VL were secondary to residue 96 in contributing to the ability of a chain to compete. Finally, unlike all previous studies, we observed a substantial number (64%) of preferred heterologous recombinations. These results are consistent with the hypothesis that the VL and VH gene rearrangements occur independently, thus resulting in random pairing of VH and VL domains.

Sequences of the genes encoding the A, B and C subunits of the Haemophilus influenzae dimethylsulfoxide reductase complex.

The genes (dms) encoding the dimethylsulfoxide reductase protein complex have been cloned and sequenced from Haemophilus influenzae (Hi) type b (Hib) strain Eagan. The Hib dms genes are arranged as an operon whose genomic organization is similar to that of the Escherichia coli (Ec) dmsABC operon. The deduced Hib DmsA, and DmsB and DmsC amino-acid sequences are highly homologous to their Ec counterparts and nearly identical to the recently published sequences of the Hi type-d strain Rd Dms proteins. Hi dimethylsulfoxide reductase appears to be a new member of the superfamily of oxidoreductase enzymes.

Routine on-line psychiatric diagnosis by computer.

With the advent of effective psychiatric treatments, greater accuracy in psychiatric diagnosis has become a vital concern for psychiatric training, research, and patient care. The authors have adapted current computer diagnostic procedures in order to obtain highly accurate diagnosis while simplifying and shortening the process of information input and diagnostic output. Their program requires a minimum of the clinician's time and provides feedback during the diagnostic process when the clinician requires it. The authors believe that routine use of this computer diagnostic program will improve psychiatric training, research, and patient care.

Computer-administered cognitive-behavioral therapy for depression.

The authors evaluated a six-session interactive computer cognitive-behavioral treatment program given to volunteer patients who met Research Diagnostic Criteria (RDC) for major or minor depressive disorder. Patients were randomly assigned to computer-administered cognitive-behavioral treatment, to therapist-administered cognitive-behavioral treatment, or to a waiting-list control condition. After treatment and at 2-month follow-up, both treatment groups had improved significantly more than control subjects in their scores on the Beck Depression Inventory, SCL-90-R depression and global scales, Hamilton Rating Scale for Depression, and Automatic Thoughts Questionnaire. The treatment groups did not differ from each other at either time.

A comparison of the Diagnostic Interview Schedule and clinical diagnosis.

The Diagnostic Interview Schedule (DIS) was administered to 220 psychiatric patients by lay interviewers. Kappas for agreement between DIS and chart diagnoses ranged from .39 to -.03 and averaged .14 for 13 diagnostic categories. Agreement was best for affective, obsessive-compulsive, and schizophrenic disorders and was poorest for phobias where patients overemphasized fears. The authors suggest that clinician evaluation of information collected by the DIS is important, especially in diagnosing individual cases.

Pretransplant crossmatch status and immunoglobulin production in renal transplant recipients.

The factors responsible for B cell regulation in stable renal transplant patients are unknown. To examine these control mechanisms, the B cell responses to 4 mitogens (pokeweed, wheat germ agglutinin, lipopolysaccharide, and SAC-1), which are known to stimulate B cells by different mechanisms, were measured in two groups of stable long-term (greater than 1 year post-transplant) renal transplant recipients. The first group were patients who had been transplanted under conditions of a negative crossmatch on all available pretransplant sera (negative crossmatch group) and the second group were patients who might have a unique regulation of B cell function in that they had been successfully transplanted under the conditions of a negative crossmatch using sera at the time of transplant but with pretransplant sera that gave a positive donor-specific T cell crossmatch (positive crossmatch group). Stable transplant patients were found to have significantly impaired responses to all four mitogens tested. Furthermore there were no differences in the responses of the negative crossmatch patients as compared with the positive crossmatch patients. The lack of response to mitogens was not due to a lack of proliferation of cells or to a loss of viability in culture. The number of cells in culture was the same in negative crossmatch patients and controls but was significantly less than controls in positive crossmatch patients (P less than 0.001). These findings suggest an intrinsic B cell defect in all stable transplant patients, and that the degree of the impaired B cell responses is the same in positive and negative crossmatch patients. In addition in positive crossmatch patients, there is a decrease in the percentage B cells that resulted after separation on a Ficoll-Paque gradient.

Production of immunogenic HIV-1 viruslike particles in stably engineered monkey cell lines.

A proviral fragment from human immunodeficiency virus type 1 (HIV-1) (LAV-1BRU) containing only protein-coding information, was expressed in COS cells using constitutive promoters in transient and stable transfection experiments. The presence of viruslike particles in cell supernatants was verified by Western blot analysis, density gradient centrifugation, and electron microscopy. Transfection of Vero cells with a similar construct employing the human metallothionein promoter led to the isolation of stable cell lines exhibiting inducible viruslike particle expression in response to cadmium chloride treatment. Induction ratios for viruslike particle expression were in excess of 1000-fold with production levels of p24 core antigen as high as 0.6 mg/L per 24 h. HIV-1 viruslike particles were immunogenic in mice, leading to strong envelope and core-specific humoral responses after two immunizations. The development of stable cell lines expressing significant quantities of HIV-1 viruslike particles offers an alternative to the use of live virus vectors for the production and evaluation of particle-based AIDS vaccines.

Proteins associated with activity of Fc receptors on isolated human placental syncytiotrophoblast microvillous plasma membranes.

To identify Fc receptors from human placental microvilli, proteins that were liberated by detergents from human placental synctiotrophoblast microvillous membranes (StMPM) were characterized by their abilities to bind human IgG in immune complexes with sheep or goat anti-human IgG and to monomeric rabbit anti-dinitrophenol (DNP) IgG bound to DNP-lysine Sepharose. Three placental IgG-binding proteins coprecipitated with immune complexes (Mr = 68,000, 52,000-56,000, 40,000) and were designated pIBP68, pIBP56 and pIBP40, respectively. Of the three proteins only pIBP56 bound to immobilized monomeric rabbit IgG. It was isolated from detergent lysates of StMPM and LDS/phenol glycoprotein extracts of placental plasma membranes suggesting that pIBP56 was a glycoprotein FcR previously reported (Mikulska et al, 1982). The binding specificities of pIBP56 and pIBP40 appeared to be detergent dependent. Photoaffinity crosslinking of StMPM surface proteins in situ to monomeric rabbit derivatized with N-succinimidyl(4-azidophenyl)-I, 3-dithiopropionate identified IgG-binding proteins identical in size to pIBP56 and pIBP40. Crosslinking further suggested that monomeric IgG covalently bound to a complex of StMPM proteins with a total size of 110,000-120,000 Mr. The findings suggest that pIBP68, pIBP56 and pIBP68 are responsible for IgG binding activity of placental StMPM.

Suicide risk prediction by computer interview: a prospective study.

A computer interview program that uses a subjective Bayesian probability model to assess suicide risk was evaluated. Predictions made by clinicians for 52 patients were compared with predictions made by the computer for the same patients. The computer was significantly (p = .001) better at predicting attempters, and clinicians were significantly (p = .01) better at predicting nonattempters. An analysis of receiver operating characteristic curves showed that the computer had better overall discrimination, but the difference was nonsignificant.