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Biomedical subjects

E Costello

Publications and source records attributed to E Costello.

At least 37 records · Page 2Linked to original sources

Restriction fragment length polymorphism analysis of Mycobacterium avium isolates from animal and human sources.

Restriction fragment length polymorphism (RFLP) analysis using probes derived from the insertion sequences IS901, IS1245 and IS1311, was carried out on Mycobacterium avium isolates obtained from 18 human patients, 44 deer, 14 pigs and five cattle in the Republic of Ireland. Forty-two of the cervine isolates and two of the bovine isolates contained IS901, while this insertion sequence was absent from all of the human and porcine isolates. RFLP analysis with IS901 probe differentiated the 44 field isolates which contained this element into three types. All of the IS901-positive isolates had a characteristic three-band IS1245 hybridisation pattern and a characteristic single-band IS1311 hybridisation pattern. The IS901-negative isolates exhibited highly polymorphic IS1245 and IS1311 hybridisation patterns which differentiated the human and porcine isolates into a wide diversity of strain types.

Animals↗

Study of restriction fragment length polymorphism analysis and spoligotyping for epidemiological investigation of Mycobacterium bovis infection.

Restriction fragment length polymorphism (RFLP) analysis with probes derived from the insertion element IS6110, the direct repeat sequence, and the polymorphic GC-rich sequence (PGRS) and a PCR-based typing method called spacer oligonucleotide typing (spoligotyping) were used to strain type Mycobacterium bovis isolates from the Republic of Ireland. Results were assessed for 452 isolates which were obtained from 233 cattle, 173 badgers, 33 deer, 7 pigs, 5 sheep, and 1 goat. Eighty-five strains were identified by RFLP analysis, and 20 strains were identified by spoligotyping. Twenty percent of the isolates were the most prevalent RFLP type, while 52% of the isolates were the most prevalent spoligotype. Both the prevalent RFLP type and the prevalent spoligotype were identified in isolates from all animal species tested and had a wide geographic distribution. Isolates of some RFLP types and some spoligotypes were clustered in regions consisting of groups of adjoining counties. The PGRS probe gave better differentiation of strains than the IS6110 or DR probes. The majority of isolates from all species carried a single IS6110 copy. In four RFLP types IS6110 polymorphism was associated with deletion of fragments equivalent in size to one or two direct variable repeat sequences. The same range and geographic distribution of strains were found for the majority of isolates from cattle, badgers, and deer. This suggests that transmission of infection between these species is a factor in the epidemiology of M. bovis infection in Ireland.

Animals↗

A study of cattle-to-cattle transmission of Mycobacterium bovis infection.

Twenty steers, positive to the single intradermal comparative tuberculin test (SICTT), were selected from herds with a recent history of Mycobacterium bovis infection. Ten steers, negative to SICTT, were selected from herds with no history of M. bovis infection and served as in-contact animals. The animals were divided into 10 groups, each consisting of two SICTT-positive (reactor) animals and one in-contact animal. Each group was housed in an individual loose-box for a period of 1 year. Five of the groups were fed a restricted diet for part of the experiment. All cattle were slaughtered at the end of the study period and examined at post mortem. Transmission of infection to an in-contact animal occurred in four of the 10 groups. One of the four in-contact animals, which became infected, had a retropharyngeal lymph node tubercle and M. bovis was isolated from lymph nodes without visible lesions from the other three. Two of the infected in-contact animals without visible lesions did not show any detectable cell-mediated immune response. There was no evidence that dietary, restriction had any effect on transmission of disease.

Animal Husbandry↗

Use of dialectical behavior therapy in a partial hospital program for women with borderline personality disorder.

Dialectical behavior therapy, an outpatient psychosocial treatment for chronically suicidal women with borderline personality disorder, has been adapted for use in a partial hospital program for women. Patients attend the program for a minimum of five days of individual and group therapy, and full census is 12 women. About 65 percent of participants meet at least three criteria for borderline personality disorder, and most have suicidal and self-injurious behavior. Their comorbid diagnoses include trauma-related diagnoses and anxiety disorders, severe eating disorders, substance abuse, and depression. The partial hospital program is linked to an aftercare program offering six months of outpatient skills training based on dialectical behavior therapy. Both programs focus on teaching patients four skills: mindfulness (attention to one's experience), interpersonal effectiveness, emotional regulation, and distress tolerance. Two years of operation of the women's partial hospital program provides promising anecdotal evidence that dialectical behavioral therapy, an outpatient approach, can be effectively modified for partial hospital settings and a more diverse population.

Adult↗

Stressors in families with a child with a chronic condition: an analysis of qualitative studies and a framework.

This article presents a comprehensive, research-based, clinically useable framework of stressors and tasks for families with a child with a chronic condition. Terms such as stressors, tasks, challenges, concerns, and problems are commonly used to describe the struggles and triumphs of these families. Their unique and changing nature has complicated comprehensive description. The steps in the early development of the Burke Stressors and Tasks Framework for Families with a Child with a Chronic Condition, and its clinical uses, are briefly described. The final step in the development of the Framework is discussed in more detail. This was a "meta-analysis" of qualitative research findings that confirmed the components of the Framework. Conclusions are drawn for subsequent research steps and clinical uses of the Framework.

Adult↗

Isolation of mycobacteria from lymph node lesions in deer.

A total of 14,842 farmed deer were slaughtered and examined postmortem in Irish abattoirs between January 1993 and September 1996. Lymph node lesions were detected in 119 deer and these were examined histopathologically and cultured. A total of 115 of the lesions were characterised as tuberculous and, on culture, Mycobacterium avium was isolated from 49 of them, M bovis from 41, unclassified mycobacteria from five, and 20 of the tuberculous lesions did not yield any isolate. Tubercles which yielded M avium on culture contained on average more acid-fast bacilli, more epithelioid macrophages and fewer Langhans giant cells than tubercles from which M bovis was isolated. Twelve lesions from feral deer culled from a national park were also examined and M bovis was isolated from nine.

Animals↗

High mobility group chromosomal protein 1 binds to the adeno-associated virus replication protein (Rep) and promotes Rep-mediated site-specific cleavage of DNA, ATPase activity and transcriptional repression.

High mobility group protein 1 (HMG1) is an abundant non-histone chromosomal protein which plays a role in several nuclear events involving DNA. Here we demonstrate that HMG1 physically interacts with the human adeno-associated virus (AAV) Rep protein. HMG1 promotes the formation of Rep-DNA complexes and stimulates the activity of Rep in site- and strand-specific cleavage of DNA and the hydrolysis of ATP, functions required for viral gene regulation, replication and site-specific integration of viral DNA into human chromosome 19. We show that HMG1 enhances Rep-mediated repression of the AAV p5 promoter in transfected cells, suggesting that HMG1 and Rep also interact in vivo. HMG1, Rep and DNA can be immunoprecipitated as a ternary complex. Kinetic studies indicate that complexes of Rep with DNA have similar stabilities in the presence and absence of HMG1. These results suggest that the effect of HMG1 on Rep binding is exerted at the step of complex formation and thereby may reflect an activity of HMG1 in promoting the assembly of complex cellular nucleoprotein structures.

Adenosine Triphosphatases↗

Performance of the single intradermal comparative tuberculin test in identifying cattle with tuberculous lesions in Irish herds.

The sensitivity of the single intradermal comparative tuberculin test, as applied in the Republic of Ireland, was estimated in 353 cattle with tuberculous lesions. These cattle had been removed from 47 herds which were depopulated owing to chronic or extensive infection with Mycobacterium bovis. The test had a sensitivity of 90.9 per cent, because 321 (90.9 per cent) of the 353 cattle with tuberculous lesions gave a positive or inconclusive result, and 32 gave a negative result. These 32 negative cattle came from 17 (36 per cent) of the 47 depopulated herds.

Animals↗

Detection of Mycobacterium bovis infection in cattle using an immunoassay for bovine soluble interleukin-2 receptor-alpha (sIL-2R-alpha) produced by peripheral blood T-lymphocytes following incubation with tuberculin PPD.

After activation of T-lymphocytes with antigen there is an increase in the expression of interleukin-2 receptor-alpha (IL-2R-alpha) followed by the release of a soluble form of the molecule (sIL-2R-alpha) from the membrane of the stimulated cells. The present study investigates the novel use of the release of sIL-2R-alpha from activated T-lymphocytes as a marker of cell-mediated immunity (CMI) in cattle infected with Mycobacterium bovis. An enzyme immunoassay was used to detect sIL-2R-alpha produced following incubation of bovine peripheral blood mononuclear cells with mycobacterial antigens. Using this assay, 63/67 cattle naturally infected with M. bovis were identified whereas only 1/51 uninfected animals were considered to give a positive result. This assay is more convenient to use than lymphocyte proliferation assays which involve the use of radionucleosides. It should prove useful for monitoring the immunological activation of bovine T-lymphocytes in a variety of situations including the development of CMI responses in cattle to novel mycobacterial antigens or potential vaccines.

Animals↗

PCR-based fingerprinting of Mycobacterium bovis isolates.

We investigated a number of PCR-based strategies for sub-typing isolates of Mycobacterium bovis. A panel of 15 PCR primers, designed from random sequences, insertion sequences and repetitive elements, were analyzed for their ability to allow differentiation between eight M. bovis isolates. PCR products were analyzed using agarose gel electrophoresis and polyacrylamide gel electrophoresis. Random primer based PCR, conducted with a variety of primers did not differentiate between isolates of M. bovis. Successful differentiation between isolates was achieved by the amplification of fragments located between DNA repetitive elements and insertion sequences of the M. bovis genome. PCR primers designed from the major polymorphic tandem repeat (MPTR) region and from insertion sequences IS6110 and IS986 allowed differentiation between isolates of M. bovis. This study is presented as a first step towards the development of PCR-based methods to differentiate between isolates.

Animals↗

The minute virus of mice (MVM) nonstructural protein NS1 induces nicking of MVM DNA at a unique site of the right-end telomere in both hairpin and duplex conformations in vitro.

The right-end telomere of replicative form (RF) DNA of the autonomous parvovirus minute virus of mice (MVM) consists of a sequence that is self-complementary except for a three nucleotide loop around the axis of symmetry and an interior bulge of three unpaired nucleotides on one strand (designated the right-end 'bubble'). This right-end inverted repeat can exist in the form of a folded-back strand (hairpin conformation) or in an extended form, base-paired to a copy strand (duplex conformation). We recently reported that the right-end telomere is processed in an A9 cell extract supplemented with the MVM nonstructural protein NS1. This processing is shown here to result from the NS1-dependent nicking of the complementary strand at a unique position 21 nt inboard of the folded-back genomic 5' end. DNA species terminating in duplex or hairpin configurations, or in a mutated structure that has lost the right-end bulge, are all cleaved in the presence of NS1, indicating that features distinguishing these structures are not prerequisites for nicking under the in vitro conditions tested. Cleavage of the hairpin structure is followed by strand-displacement synthesis, generating the right-end duplex conformation, while processing of the duplex structure leads to the release of free right-end telomeres. In the majority of molecules, displacement synthesis at the right terminus stops a few nucleotides before reaching the end of the template strand, possibly due to NS1 which is covalently bound to this end. A fraction of the right-end duplex product undergoes melting and re-folding into hairpin structures (formation of a 'rabbit-ear' structure).

Animals↗

The long-term sequelae of sexual abuse: support for a complex posttraumatic stress disorder.

This study examined the relationship between childhood sexual abuse and symptoms of a newly proposed complex posttraumatic stress disorder or disorder of extreme stress not otherwise specified (DESNOS). Compared to 34 women without histories of sexual abuse, 74 survivors of sexual abuse showed increased severity on DESNOS symptoms of somatization, dissociation, hostility, anxiety, alexithymia, social dysfunction, maladaptive schemas, self-destruction and adult victimization. In addition, a logistic regression found that a complex of symptoms representing DESNOS was significantly related to a history of sexual abuse. Consistent with other studies, the results of this study provide support for the idea that symptoms of DESNOS characterize survivors of sexual abuse.

Adult↗

The validation of the Trauma Symptom Checklist-40 (TSC-40) in a sample of inpatients.

This study examined the construct validity of the Trauma Symptom Checklist-40 (TSC-40; Elliot & Briere, 1992) in a sample of 130 female psychiatric inpatients. Consistent with other findings, the TSC-40 displayed criterion-related validity in relation to childhood sexual abuse. Survivors of sexual abuse obtained significantly higher scores than those without such a history on the overall TSC-40 and on each of the six subscales, except the Depression subscale. Convergent validity of three subscales was demonstrated, and divergent validity on the total TSC-40 and each of its subscales was established. Further, among a range of abuse-effects measures, the Sexual Abuse Trauma Index (SATI) subscale was the most powerful predictor of sexual abuse. The SATI and Dissociation subscales were the subscales most sensitive to the specific features of the sexual abuse.

Adolescent↗

The mismatched nucleotides in the 5'-terminal hairpin of minute virus of mice are required for efficient viral DNA replication.

The 5'-terminal sequence in the DNA of the parvovirus minute virus of mice (MVM) is a palindrome. It can form a hairpin, the stem of which is entirely base-paired except for three consecutive unpaired nucleotides which form a bubble. Since this structure is well conserved among different parvoviruses, we examined its importance for viral replication by generating MVM mutants with alterations in this region. A clone of MVMp DNA which contained the entire 3' end and more than half of the 5' palindrome was made. Although it lacked the sequence information to form a wild-type bubble, this DNA was infectious. On transfection into A9 fibroblasts, it gave rise to a virus (MVMs) which had a bubble in its 5' palindrome. The bubble consisted of four mismatched nucleotides in the same location as the unpaired nucleotides of the wild-type palindrome. Apparently, neighboring plasmid sequences were incorporated into the viral DNA, enabling formation of the mismatch. This observation suggested that a bubble is critical for growth of MVM but that its sequence is not. To find out whether MVM lacking a bubble in the 5' palindrome is viable, we made a second clone in which the plasmid sequences incorporated in MVMs were removed. Transfection of this DNA gave rise to a virus (MVMx) in which the nucleotides unpaired in the wild-type hairpin are now fully base-paired. Although MVMx can be propagated, it is defective in comparison with wild-type MVMp; it exhibited about a 50-fold-lower ratio of plaque-forming units to DNA content. In mixed infections, MVMp consistently outgrew the bubbleless MVMx. The rate of accumulation of DNA replication intermediates was lower for MVMx than for the wild-type virus. Quantitative analysis of the 5' termini of replicative form DNA suggested that the ability of MVMx to convert hairpin 5' termini to extended termini is impaired. In contrast, the virus with the altered bubble, MVMs, behaved like the wild-type MVMp in all the assays. We conclude that MVM lacking a bubble in its 5'-terminal DNA hairpin is less infectious than and has a selective disadvantage compared with wild-type MVM. The nucleotide sequence of the bubble is not critical. We provide evidence that the presence of a bubble is necessary for efficient viral DNA replication.

Animals↗

Protein kinase A and AP-1 (c-Fos/JunD) are induced during apoptosis of mouse mammary epithelial cells.

At weaning the mammary gland undergoes a reductive remodelling process (involution) which is associated with the cessation of milk protein gene expression and programmed cell death of milk-producing epithelial cells. Elevated nuclear protein kinase A (PKA) activity was observed from one day post-lactation, paralleled by increased c-fos, junB, junD and to a lesser extent c-jun mRNA levels. AP-1 DNA binding activity was transiently induced and the AP-1 complex was shown to consist principally of cFos/JunD. Oct-1 DNA binding activity and Oct-1 protein were gradually lost from the gland over the first 4 days of involution, whereas Oct-1 mRNA levels remained unchanged. Comparing nuclear extracts from normal mammary glands with nuclear extracts from glands which had been cleared of all epithelial cells 3 weeks after birth, revealed that PKA activation, AP-1 induction and Oct-1 inactivation all are dependent on the presence of the epithelial compartment. The increased Fos/Jun expression and the inactivation of Oct-1 may be consequences of the increased PKA activity. A similar induction of AP-1 (cFos/JunD) was also observed in the involuting rat ventral prostate pointing to a possible role for AP-1 in programmed cell death.

Animals↗

Efficacy of applied relaxation and cognitive-behavioral therapy in the treatment of generalized anxiety disorder.

Nondirective (ND), applied relaxation (AR), and cognitive behavioral (CBT) therapies for generalized anxiety disorder (GAD) were compared. The latter 2 conditions were generally equivalent in outcome but superior to ND at postassessment. The 3 conditions did not differ on several process measures, and ND created the greatest depth of emotional processing. Follow-up results indicated losses in gains in ND, maintained gains in the other 2 conditions, especially CBT, and highest endstate functioning for CBT. AR and CBT thus contain active ingredients in the treatment of GAD; support exists for further development of imagery exposure methods or cognitive therapy because of their likely role in promoting maintenance of change with this disorder. Expectancy for improvement was also associated with outcome, suggesting the need for further research on this construct for understanding the nature of GAD and its amelioration.

Adaptation, Psychological↗